2023/05/19 更新

写真a

カトウ ヒロノリ
加藤 裕教
KATOH HIRONORI
担当
大学院理学研究科 生物化学専攻 教授
理学部 生物化学科
職名
教授
所属
理学研究院
所属キャンパス
中百舌鳥キャンパス

担当・職階

  • 大学院理学研究科 生物化学専攻 

    教授  2023年04月 - 継続中

  • 理学部 生物化学科 

    教授  2023年04月 - 継続中

取得学位

  • 博士(薬学) ( 京都大学 )

  • 修士(薬学) ( 京都大学 )

  • 学士(薬学) ( 京都大学 )

研究分野

  • ライフサイエンス / 薬系衛生、生物化学

  • ライフサイエンス / 細胞生物学

  • ライフサイエンス / 機能生物化学

  • ライフサイエンス / 分子生物学

研究キーワード

  • 低分子量G蛋白質

  • フェロトーシス

  • シグナル伝達

  • グルコース代謝

  • アミノ酸代謝

所属学協会

  • 日本癌学会

  • 日本薬学会

  • 日本生化学会

委員歴(学外)

  • 学術誌編集委員   日本薬学会  

    2023年04月 - 継続中 

  • 近畿支部 幹事   日本生化学会  

    2018年09月 - 継続中 

  • 生化学企画委員   日本生化学会  

    2014年01月 - 2019年12月 

  • 生化学企画協力委員   日本生化学会  

    2009年01月 - 2013年12月 

受賞歴

  • 生化学会奨励賞

    2011年09月   日本生化学会  

職務経歴(学外)

  • 岐阜大学 工学部 非常勤講師

    2016年08月 - 2017年03月

  • 京都大学大学院 生命科学研究科 准教授

    2007年04月 - 2023年03月

  • 京都大学大学院 生命科学研究科 助教授

    2004年03月 - 2007年03月

  • 京都大学大学院 生命科学研究科 助手

    1999年04月 - 2004年03月

  • 京都大学大学院 薬学研究科 助手

    1997年12月 - 1999年03月

  • 日本学術振興会 特別研究員(DC1)

    1996年04月 - 1997年11月

▼全件表示

学歴

  • 京都大学   薬学研究科   博士課程   中退

    1996年04月 - 1997年11月

  • 京都大学   薬学研究科   修士課程   卒業・修了

    1994年04月 - 1996年03月

  • 京都大学   薬学部   薬学科   学士課程   卒業・修了

    1990年04月 - 1994年03月

論文

  • Expression of gamma-glutamyltransferase 1 in glioblastoma cells confers resistance to cystine deprivation–induced ferroptosis 査読

    Kazuki Hayashima, Hironori Katoh

    Journal of Biological Chemistry   298 ( 3 )   101703 - 101703   2022年03月( ISSN:0021-9258

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    担当区分:最終著者, 責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jbc.2022.101703

  • Filamin A forms a complex with EphA2 and regulates EphA2 serine 897 phosphorylation and glioblastoma cell proliferation 査読

    Yuho Tamura, Yuta Nakamizo, Yuzo Watanabe, Ikuo Kimura, Hironori Katoh

    Biochemical and Biophysical Research Communications   597   64 - 70   2022年03月( ISSN:0006-291X

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    担当区分:最終著者, 責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbrc.2022.01.050

  • Rnd2 differentially regulates oligodendrocyte myelination at different developmental periods. 査読

    Yuki Miyamoto, Tomohiro Torii, Miho Terao, Shuji Takada, Akito Tanoue, Hironori Katoh, Junji Yamauchi

    Molecular biology of the cell   32 ( 8 )   769 - 787   2021年02月

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    In the CNS, oligodendrocyte precursor cells differentiate into oligodendrocytes to wrap their plasma membranes around neuronal axons, generating mature neural networks with myelin sheaths according to spatial and temporal patterns. While myelination is known to be one of the most dynamic cell morphological changes, the overall intrinsic and extrinsic molecular cues controlling myelination remain to be fully clarified. Here, we describe the biphasic roles of Rnd2, an atypical branch of the Rho family GTPase, in oligodendrocyte myelination during development and after maturation in mice. Compared with littermate controls, oligodendrocyte-specific Rnd2 knockout mice exhibit decreased myelin thickness at the onset of myelination but increased myelin thickness in the later period. Larger proportions of Rho kinase and its substrate Mbs, the signaling unit that negatively regulates oligodendrocyte myelination, are phosphorylated at the onset of myelination, while their smaller proportions are phosphorylated in the later period. In addition, we confirm the biphasic role of Rnd2 through experiments with oligodendrocyte-specific Rnd2 transgenic mice. We conclude that Rnd2 positively regulates myelination in the early myelinating period and negatively regulates myelination in the later period. This unique modulator thus plays different roles depending on the myelination period.

    DOI: 10.1091/mbc.e20-05-0332

    DOI: 10.1091/mbc.E20-05-0332

    PubMed

  • Role of ferritinophagy in cystine deprivation-induced cell death in glioblastoma cells 査読

    Kazuki Hayashima, Ikuo Kimura, Hironori Katoh

    Biochemical and Biophysical Research Communications   539   56 - 63   2021年02月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbrc.2020.12.075

  • Epidermal growth factor promotes glioblastoma cell death under glucose deprivation via upregulation of xCT (SLC7A11). 査読

    Marina Yamamotoa, Koji Teramotoa, Hironori Katoh

    Cellular signalling   78   109874   2020年12月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    The cystine/glutamate antiporter xCT (SLC7A11) is frequently overexpressed in many cancers, including glioblastoma. Cystine taken up by the cells via xCT is reduced to cysteine, which is used to synthesize glutathione for antioxidant cellular defense. However, overexpression of xCT causes cell death under glucose-limited conditions. We found that stimulation of glioblastoma cells with epidermal growth factor (EGF) induces the upregulation of xCT and promotes cell death under glucose deprivation. Treatment with the mTOR inhibitor Torin 1 suppressed the EGF-induced upregulation of xCT and cell death. EGF increased xCT mRNA levels, which was suppressed by Torin 1. The lysosome inhibitor bafilomycin A1 increased xCT protein levels in the absence of EGF or in the presence of EGF and Torin 1. Taken together, our study suggests that EGF promotes glioblastoma cell death under glucose-limited conditions via the upregulation of xCT at transcriptional and protein levels in an mTOR-dependent manner.

    DOI: 10.1016/j.cellsig.2020.109874

    PubMed

  • High cell density increases glioblastoma cell viability under glucose deprivation via degradation of the cystine/glutamate transporter xCT (SLC7A11) 査読

    Itsuki Yamaguchi, Shige H. Yoshimura, Hironori Katoh

    Journal of Biological Chemistry   295 ( 20 )   6936 - 6945   2020年05月( ISSN:0021-9258

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.RA119.012213

  • The cystine/glutamate antiporter xCT is a key regulator of EphA2 S897 phosphorylation under glucose-limited conditions 査読

    Koji Teramoto, Hironori Katoh

    Cellular Signalling   62   109329 - 109329   2019年10月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cellsig.2019.05.014

  • EphA3 is up-regulated by epidermal growth factor and promotes formation of glioblastoma cell aggregates. 査読

    Toyama, M, Hamaoka, Y, Katoh, H

    Biochemical and Biophysical Research Communications   508 ( 3 )   715 - 721   2019年01月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

  • RasGRF1 mediates brain-derived neurotrophic factor-induced axonal growth in primary cultured cortical neurons. 査読

    Umeda K, Negishi, M, Katoh, H

    Biochemistry and Biophysics Reports   17   56 - 64   2019年

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

  • Tyrosine kinase activity of EphA2 promotes its S897 phosphorylation and glioblastoma cell proliferation 査読

    Yuho Hamaoka, Manabu Negishi, Hironori Katoh

    Biochemical and Biophysical Research Communications   499 ( 4 )   920 - 926   2018年05月( ISSN:1090-2104

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    EphA2, a member of the Eph family of receptor tyrosine kinases, has been reported to promote tumor malignancy through phosphorylation of serine 897 (S897). Here, we found that overexpression of wild-type EphA2 induced S897 phosphorylation through ERK activation without growth factors or cytokines and promoted glioblastoma cell proliferation. However, overexpression of a kinase-inactive mutant of EphA2 failed to induce ERK activation, S897 phosphorylation, and promotion of glioblastoma cell proliferation. These data suggest that when overexpressed, EphA2 induces ERK activation through its tyrosine kinase activity, leading to S897 phosphorylation and promotion of glioblastoma cell proliferation. Our findings provide a new insight into how EphA2 mediates glioblastoma progression.

    DOI: 10.1016/j.bbrc.2018.04.020

  • Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation 査読

    Takeo Goji, Kazuhiko Takahara, Manabu Negishi, Hironori Katoh

    JOURNAL OF BIOLOGICAL CHEMISTRY   292 ( 48 )   19721 - 19732   2017年12月( ISSN:0021-9258

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Oncogenic signaling in cancer cells alters glucose uptake and utilization to supply sufficient energy and biosynthetic intermediates for survival and sustained proliferation. Oncogenic signaling also prevents oxidative stress and cell death caused by increased production of reactive oxygen species. However, elevated glucose metabolism in cancer cells, especially in glioblastoma, results in the cells becoming sensitive to glucose deprivation (i.e. in high glucose dependence), which rapidly induces cell death. However, the precise mechanism of this type of cell death remains unknown. Here, we report that glucose deprivation alone does not trigger glioblastoma cell death. We found that, for cell death to occur in glucose-deprived glioblastoma cells, cystine and glutamine also need to be present in culture media. We observed that cystine uptake through the cystine/glutamate antiporter xCT under glucose deprivation rapidly induces NADPH depletion, reactive oxygen species accumulation, and cell death. We conclude that although cystine uptake is crucial for production of antioxidant glutathione in cancer cells its transport through xCT also induces oxidative stress and cell death in glucose-deprived glioblastoma cells. Combining inhibitors targeting cancer-specific glucose metabolism with cystine and glutamine treatment may offer a therapeutic approach for glioblastoma tumors exhibiting high xCT expression.

    DOI: 10.1074/jbc.M117.814392

  • EphA2 is a key effector of the MEK/ERK/RSK pathway regulating glioblastoma cell proliferation 査読

    Yuho Hamaoka, Manabu Negishi, Hironori Katoh

    CELLULAR SIGNALLING   28 ( 8 )   937 - 945   2016年08月( ISSN:0898-6568

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    EphA2, a member of the Eph receptor tyrosine kinases, is frequently overexpressed in a variety of malignancies, including glioblastoma, and its expression is correlated with poor prognosis. EphA2 acts as a tumor promoter through a ligand ephrin-independent mechanism, which requires phosphorylation of EphA2 on serine 897 (S897), leading to increased cell migration and invasion. In this study, we show that ligand-independent EphA2 signaling occurs downstream of the MEK/ERK/RSK pathway and mediates epidermal growth factor (EGF)-induced cell proliferation in glioblastoma cells. Suppression of EphA2 expression by long-term exposure to ligand ephrinA1 or EphA2-targeted shRNA inhibited EGF-induced cell proliferation. Stimulation of the cells with EGF induced EphA2 5897 phosphorylation, which was suppressed by MEK and RSK inhibitors, but not by phosphatidylinositol 3-kinase (PI3K) and Akt inhibitors. The RSK inhibitor or RSK2-targeted shRNA also suppressed EGF-induced cell proliferation. Furthermore, overexpression of wild-type EphA2 promoted cell proliferation without EGF stimulation, whereas overexpression of EphA2-S897A mutant suppressed EGF- or RSK2-induced proliferation. Taken together, these results suggest that EphA2 is a key downstream target of the MEK/ERK/RSK signaling pathway in the regulation of glioblastoma cell proliferation. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cellsig.2016.04.009

    J-GLOBAL

  • Tyrosine Phosphorylation of SGEF Regulates RhoG Activity and Cell Migration 査読

    Yusuke Okuyama, Kentaro Umeda, Manabu Negishi, Hironori Katoh

    PLOS ONE   11 ( 7 )   2016年07月( ISSN:1932-6203

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    SGEF and Ephexin4 are members of the Ephexin subfamily of RhoGEFs that specifically activate the small GTPase RhoG. It is reported that Ephexin1 and Ephexin5, two well-characterized Ephexin subfamily RhoGEFs, are tyrosine-phosphorylated by Src, and that their phosphorylation affect their activities and functions. In this study, we show that SGEF, but not Ephexin4, is tyrosine-phosphorylated by Src. Tyrosine phosphorylation of SGEF suppresses its interaction with RhoG, the elevation of RhoG activity, and SGEF-mediated promotion of cell migration. We identified tyrosine 530 (Y530), which is located within the Dbl homology domain, as a major phosphorylation site of SGEF by Src, and Y530F mutation blocked the inhibitory effect of Src on SGEF. Taken together, these results suggest that the activity of SGEF is negatively regulated by tyrosine phosphorylation of the DH domain.

    DOI: 10.1371/journal.pone.0159617

    J-GLOBAL

  • Eph/ephrin reverse signalling induces axonal retraction through RhoA/ROCK pathway 査読

    Shingo Takeuchi, Hironori Katoh, Manabu Negishi

    JOURNAL OF BIOCHEMISTRY   158 ( 3 )   245 - 252   2015年09月( ISSN:0021-924X

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    掲載種別:研究論文(学術雑誌)  

    Eph/ephrin signalling plays essential roles in various tissue developments, such as axon guidance, angiogenesis and tissue separation. Interaction between Ephs and ephrins upon cell-cell contact results in forward (towards Eph-expressing cells) and reverse (towards ephrin-expressing cells) signalling. Although the molecular mechanisms downstream of Eph/ephrin forward signalling have been extensively studied, the functions and intracellular molecular mechanisms of Eph/ephrin reverse signalling are not fully understood. Rho GTPases are key regulators of the actin cytoskeleton to regulate cell morphology. In this study, we revealed that stimulation with the extracellular domain of EphB2 to activate Eph/ephrin reverse signalling induced axonal retraction in hippocampal neurons. The reduction of axonal length and branching by Eph/ephrin reverse signalling was blocked by inhibition of RhoA or Rho-associated coiled-coil-containing protein kinase (ROCK). These results suggest that Eph/ephrin reverse signalling negatively regulates axonal outgrowth and branching through RhoA/ROCK pathway in hippocampal neurons.

    DOI: 10.1093/jb/mvv042

  • HGF-induced serine 897 phosphorylation of EphA2 regulates epithelial morphogenesis of MDCK cells in 3D culture 査読

    Kohei Harada, Manabu Negishi, Hironori Katoh

    JOURNAL OF CELL SCIENCE   128 ( 10 )   1912 - 1921   2015年05月( ISSN:0021-9533

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Expression of EphA2 is upregulated in various cancers that are derived from epithelial cells and correlates with the ability of a cancer cell to undergo migration and invasion. Here we have investigated the role of EphA2 in the epithelial morphogenesis of Madin-Darby canine kidney (MDCK) cells in three-dimensional culture. We show that EphA2 is phosphorylated on serine residue 897 through hepatocyte growth factor (HGF) stimulation using a phosphatidylinositol 3-kinase (PI3K)-Akt-dependent mechanism and that this phosphorylation is required for the formation of extensions, the first step of tubulogenesis, in MDCK cysts. By contrast, stimulation using the ligand ephrinA1 dephosphorylates EphA2 on serine residue 897 and suppresses the HGF-induced morphological change. Furthermore, activation of the small GTPase RhoG is involved in the HGF-induced formation of extensions downstream of EphA2. These observations suggest that a ligand-independent activity of EphA2 contributes to epithelial morphogenesis.

    DOI: 10.1242/jcs.163790

  • EphB6 promotes anoikis by modulating EphA2 signaling 査読

    Mai Akada, Kohei Harada, Manabu Negishi, Hironori Katoh

    CELLULAR SIGNALLING   26 ( 12 )   2879 - 2884   2014年12月( ISSN:0898-6568

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Anoikis is a specific type of apoptosis induced by detachment of epithelial cells from extracellular matrix, and acquiring resistance to anoikis is an important step that enables cancer cells to metastasize. EphA2, which is overexpressed in a variety of human cancers, is phosphorylated by Akt on serine 897 and mediates ligand ephrin-independent promotion of anoikis resistance through the RhoG activator Ephexin4. EphB6 is frequently silenced in invasive and metastatic cancers; however, its role in cancer progression is poorly understood. Here we show that EphB6 interacts with EphA2 and suppresses EphA2-mediated promotion of anoikis resistance in MCF7 breast cancer cells. On the other hand, knockdown of EphB6 promotes anoikis resistance. We further show that expression of EphB6 decreases serine 897 phosphorylation of EphA2 and suppresses EphA2-Ephexin4 interaction and the RhoG activation. These findings implicate EphB6 as a negative regulator of EphA2 oncogenic signaling. (C) 2014 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cellsig.2014.08.031

  • Dock4 forms a complex with SH3YL1 and regulates cancer cell migration 査読

    Masakazu Kobayashi, Kohei Harada, Manabu Negishi, Hironori Katoh

    CELLULAR SIGNALLING   26 ( 5 )   1082 - 1088   2014年05月( ISSN:0898-6568

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Dock4 is a member of the Dock180 family of proteins that mediates cancer cell migration through activation of Rac. However, the regulatory mechanism of Dock4 remains unclear. In this study, we show that the C-terminal praline-rich region of Dock4 is essential for the Dock4 mediated promotion of cell migration in MDA-MB-231 breast cancer cells. We found that a phosphoinositide-binding protein SH3YL1 interacted with the C-terminal praline-rich region of Dock4. Interaction of SH3YL1 with Dock4 promoted Dock4-mediated Rac1 activation and cell migration. Mutations in the phosphoinositide-binding domain disrupted the ability of SH3YL1 to promote Dock4-mediated cell migration. In addition, depletion of SH3YL1 in MDA-MB-231 cells suppressed cell migration. Taken together, these results provide evidence for a novel and functionally important interaction between Dock4 and SH3YL1 to promote cancer cell migration by regulating Rac1 activity. (C) 2014 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cellsig.2014.01.027

  • Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation 査読

    Shuhei Ueda, Manabu Negishi, Hironori Katoh

    MOLECULAR BIOLOGY OF THE CELL   24 ( 10 )   1602 - 1613   2013年05月( ISSN:1059-1524

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    In neuronal development, dendritic spine formation is important for the establishment of excitatory synaptic connectivity and functional neural circuits. Developmental deficiency in spine formation results in multiple neuropsychiatric disorders. Dock4, a guanine nucleotide exchange factor (GEF) for Rac, has been reported as a candidate genetic risk factor for autism, dyslexia, and schizophrenia. We previously showed that Dock4 is expressed in hippocampal neurons. However, the functions of Dock4 in hippocampal neurons and the underlying molecular mechanisms are poorly understood. Here we show that Dock4 is highly concentrated in dendritic spines and implicated in spine formation via interaction with the actin-binding protein cortactin. In cultured neurons, short hairpin RNA (shRNA)-mediated knockdown of Dock4 reduces dendritic spine density, which is rescued by coexpression of shRNA-resistant wild-type Dock4 but not by a GEF-deficient mutant of Dock4 or a truncated mutant lacking the cortactin-binding region. On the other hand, knockdown of cortactin suppresses Dock4-mediated spine formation. Taken together, the results show a novel and functionally important interaction between Dock4 and cortactin for regulating dendritic spine formation via activation of Rac.

    DOI: 10.1091/mbc.E12-11-0782

    PubMed

  • Ephexin4-mediated promotion of cell migration and anoikis resistance is regulated by serine 897 phosphorylation of EphA2 査読

    Hiromu Kawai, Masakazu Kobayashi, Nao Hiramoto-Yamaki, Kohei Harada, Manabu Negishi, Hironori Katoh

    FEBS OPEN BIO   3   78 - 82   2013年( ISSN:2211-5463

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    EphA2 is activated through phosphorylation on serine 897 (S897) by Ala to promote cancer cell motility and invasion, independently of stimulation by ephrin, its ligand. Here we show that S897 phosphorylation of EphA2 strengthens the interaction between EphA2 and Ephexin4, a guanine nucleotide exchange factor for the small GTPase RhoG. S897A mutation of EphA2 abolished the EphA2 Ephexin4-mediated RhoG activation, promotion of cell migration, and resistance to anoikis. Our results suggest that S897-phosphorylated EphA2 recruits Ephexin4 to promote cell migration and anoikis resistance, providing a molecular link between S897 phosphorylation of EphA2 and tumor progression. (C) 2013 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. All rights reserved.

    DOI: 10.1016/j.fob.2013.01.002

    PubMed

  • The RhoG signaling pathway 査読

    Hironori Katoh

    Seikagaku   84 ( 7 )   539 - 550   2012年( ISSN:0037-1017

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  • The F-BAR Protein Rapostlin Regulates Dendritic Spine Formation in Hippocampal Neurons 査読

    Yohei Wakita, Tetsuhiro Kakimoto, Hironori Katoh, Manabu Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   286 ( 37 )   32672 - 32683   2011年09月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Pombe Cdc15 homology proteins, characterized by Fer/CIP4 homology Bin-Amphiphysin-Rvs/extended Fer/CIP4 homology (F-BAR/EFC) domains with membrane invaginating property, play critical roles in a variety of membrane reorganization processes. Among them, Rapostlin/formin-binding protein 17 (FBP17) has attracted increasing attention as a critical coordinator of endocytosis. Here we found that Rapostlin was expressed in the developing rat brain, including the hippocampus, in late developmental stages when accelerated dendritic spine formation and maturation occur. In primary cultured rat hippocampal neurons, knockdown of Rapostlin by shRNA or overexpression of Rapostlin-QQ, an F-BAR domain mutant of Rapostlin that has no ability to induce membrane invagination, led to a significant decrease in spine density. Expression of shRNA-resistant wild-type Rapostlin effectively restored spine density in Rapostlin knockdown neurons, whereas expression of Rapostlin deletion mutants lacking the protein kinase C-related kinase homology region 1 (HR1) or Src homology 3 (SH3) domain did not. In addition, knockdown of Rapostlin or overexpression of Rapostlin-QQ reduced the uptake of transferrin in hippocampal neurons. Knockdown of Rnd2, which binds to the HR1 domain of Rapostlin, also reduced spine density and the transferrin uptake. These results suggest that Rapostlin and Rnd2 cooperatively regulate spine density. Indeed, Rnd2 enhanced the Rapostlin-induced tubular membrane invagination. We conclude that the F-BAR protein Rapostlin, whose activity is regulated by Rnd2, plays a key role in spine formation through the regulation of membrane dynamics.

    DOI: 10.1074/jbc.M111.236265

    PubMed

  • Ephexin4 and EphA2 mediate resistance to anoikis through RhoG and phosphatidylinositol 3-kinase 査読

    Kohei Harada, Nao Hiramoto-Yamaki, Manabu Negishi, Hironori Katoh

    EXPERIMENTAL CELL RESEARCH   317 ( 12 )   1701 - 1713   2011年07月( ISSN:0014-4827

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Disruption of cell-extracellular matrix interaction causes epithelial cells to undergo apoptosis called anoikis, and resistance to anoikis has been suggested to be a critical step for cancer cells to metastasize. EphA2 is frequently overexpressed in a variety of human cancers, and recent studies have found that overexpression of EphA2 contributes to malignant cellular behavior, including resistance to anoikis, in several different types of cancer cells. Here we show that Ephexin4, a guanine nucleotide exchange factor for the small GTPase RhoG that interacts with EphA2, plays an important role in the regulation of anoikis. Knockdown of Ephexin4 promoted anoikis in HeLa cells, and experiments using a knockdown-rescue approach showed that activation of RhoG, phosphatidylinositol 3-kinase (PI3K), and Akt was required for the Ephexin4-mediated suppression of anoikis. Indeed, Ephexin4 knockdown caused a decrease in RhoG activity and Akt phosphorylation in HeLa cells cultured in suspension. In addition, Ephexin4 was involved in the EphA2-mediated suppression of anoikis. Taken together, these results suggest that Ephexin4 mediates resistance to anoikis through activation of RhoG and PI3K downstream of EphA2. (c) 2011 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.yexcr.2011.05.014

    PubMed

    J-GLOBAL

  • Semaphorin 4D/Plexin-B1 Stimulates PTEN Activity through R-Ras GTPase-activating Protein Activity, Inducing Growth Cone Collapse in Hippocampal Neurons 査読

    Izumi Oinuma, Yuri Ito, Hironori Katoh, Manabu Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   285 ( 36 )   28200 - 28209   2010年09月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Plexins are receptors for axonal guidance molecules semaphorins. We recently reported that the semaphorin 4D (Sema4D) receptor, Plexin-B1, suppresses PI3K signaling through the R-Ras GTPase-activating protein (GAP) activity, inducing growth cone collapse. Phosphatidylinositol 3-phosphate level is critically regulated by PI3K and PTEN (phosphatase and tensin homologue deleted chromosome ten). Here we examined the involvement of PTEN in the Plexin-B1-induced repulsive response. Phosphorylation of PTEN at Ser-380 is known to suppress its phosphatase activity. Sema4D induced the dephosphorylation of PTEN at Ser-380 and stimulated PTEN phosphatase activity in hippocampal neurons. Knockdown of endogenous PTEN suppressed the Sema4D-induced growth cone collapse. Phosphorylation mimic PTEN mutant suppressed the Sema4D-induced growth cone collapse, whereas phosphorylation-resistant PTEN mutant by itself induced growth cone collapse. Plexin-B1-induced PTEN dephosphorylation through R-Ras GAP activity and R-Ras GAP activity was by itself sufficient for PTEN dephosphorylation and activation. We also suggested that the Sema4D-induced PTEN dephosphorylation and growth cone collapse were mediated by the inhibition of casein kinase 2 alpha activity. Thus, we propose that Sema4D/Plexin-B1 promotes the dephosphorylation and activation of PTEN through the R-Ras GAP activity, inducing growth cone collapse.

    DOI: 10.1074/jbc.M110.147546

    PubMed

    J-GLOBAL

  • Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism 査読

    Nao Hiramoto-Yamaki, Shingo Takeuchi, Shuhei Ueda, Kohei Harada, Satoshi Fujimoto, Manabu Negishi, Hironori Katoh

    Journal of Cell Biology   190 ( 3 )   461 - 477   2010年08月( ISSN:0021-9525

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    EphA2, a member of the Eph receptor family, is frequently overexpressed in a variety of human cancers, including breast cancers, and promotes cancer cell motility and invasion independently of its ligand ephrin stimulation. In this study, we identify Ephexin4 as a guanine nucleotide exchange factor (GEF) for RhoG that interacts with EphA2 in breast cancer cells, and knockdown and rescue experiments show that Ephexin4 acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. The activation of RhoG recruits its effector ELMO2 and a Rac GEF Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. In addition, the Dock4-mediated Rac activation is required for breast cancer cell migration. Our findings reveal a novel link between EphA2 and Rac activation that contributes to the cell motility and invasiveness of breast cancer cells.

    DOI: 10.1083/jcb.201005141

    PubMed

    J-GLOBAL

  • RhoG Promotes Neural Progenitor Cell Proliferation in Mouse Cerebral Cortex 査読

    Satoshi Fujimoto, Manabu Negishi, Hironori Katoh

    MOLECULAR BIOLOGY OF THE CELL   20 ( 23 )   4941 - 4950   2009年12月( ISSN:1059-1524

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    In early cortical development, neural progenitor cells (NPCs) expand their population in the ventricular zone (VZ), and produce neurons. Although a series of studies have revealed the process of neurogenesis, the molecular mechanisms regulating NPC proliferation are still largely unknown. Here we found that RhoG, a member of Rho family GTPases, was expressed in the VZ at early stages of cortical development. Expression of constitutively active RhoG promoted NPC proliferation and incorporation of bromodeoxyuridine (BrdU) in vitro, and the proportion of Ki67-positive cells in vivo. In contrast, knockdown of RhoG by RNA interference suppressed the proliferation, BrdU incorporation, and the proportion of Ki67-positive cells in NPCs. However, knockdown of RhoG did not affect differentiation and survival of NPC. The RhoG-induced promotion of BrdU incorporation required phosphatidylinositol 3-kinase (PI3K) activity but not the interaction with ELMO. Taken together, these results indicate that RhoG promotes NPC proliferation through PI3K in cortical development.

    DOI: 10.1091/mbc.E09-03-0200

    PubMed

  • Regulation of Dendrite Growth by the Cdc42 Activator Zizimin1/Dock9 in Hippocampal Neurons 査読

    Kazuya Kuramoto, Manabu Negishi, Hironori Katoh

    JOURNAL OF NEUROSCIENCE RESEARCH   87 ( 8 )   1794 - 1805   2009年06月( ISSN:0360-4012

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Rho family small GTPases are key regulators of morphological changes in neurons. Cdc42, one of the most characterized members of the Rho family of proteins, is involved in axon and dendrite outgrowth through cytoskeletal reorganization. Recent studies have identified Zizimin1, a member of the Dock180-related family of proteins [also called CDM (Ced-5/Dock180/Myoblast city)-zizimin homology (CZH) proteins], as a specific guanine-nucleotide exchange factor (GEF) for Cdc42. However, the physiological function of Zizimin1 is totally unknown. In this study, we investigated the role of Zizimin1 in dendrite development in rat hippocampal neurons. In situ hybridization and Western blot analysis showed that Zizimin1 is strongly expressed in the developing brain including in the hippocampus and cerebral cortex in late developmental stages. Overexpression of wild-type Zizimin1 promoted dendrite growth, whereas knockdown of Zizimin1 by short hairpin RNA or expression of a mutant Zizimin1 lacking Cdc42 GEF activity suppressed dendrite growth in primary cultured rat hippocampal neurons. Both the N-terminal CZH1 domain, which is conserved among CZH proteins, and the Pleckstrin homology domain of Zizimin1 are involved in membrane localization, Cdc42 activation, and regulation of dendrite growth. Thus, these results suggest that Zizimin1 plays an important role in dendrite growth in hippocampal neurons through activation of Cdc42. (C) 2009 Wiley-Liss, Inc.

    DOI: 10.1002/jnr.21997

    PubMed

  • β2-Chimaerin binds to EphA receptors and regulates cell migration 査読

    S. Takeuchi, N. Yamaki, T. Iwasato, M. Negishi, H. Katoh

    FEBS Letters   583 ( 8 )   1237 - 1242   2009年04月( ISSN:0014-5793

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.febslet.2009.03.032

    PubMed

    J-GLOBAL

  • Different Requirement for Rnd GTPases of R-Ras GAP Activity of Plexin-C1 and Plexin-D1 査読

    Kanami Uesugi, Izumi Oinuma, Hironori Katoh, Manabu Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   284 ( 11 )   6743 - 6751   2009年03月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Plexins, comprising Plexin-A, -B, -C, and -D subfamilies, are receptors for semaphorins governing cell adhesion, migration, and axon guidance. Among plexin subfamilies, Plexin-A1 and Plexin-B1 have been shown to function as an R-Ras GAP, inducing repulsive responses, and the expression of R-Ras GAP activity requires the binding of Rnd1, a member of Rnd subfamily of Rho GTPases. However, signaling pathways of Plexin-D1 and Plexin-C1 still remain obscure. Here, we found that Plexin-D1 displayed R-Ras GAP activity and inhibited migration of COS-7 cells, and these actions required Rnd2, another Rnd subfamily GTPase. Rnd2 bound to Plexin-D1 in cortical neurons, and Sema3E/Plexin-D1-induced inhibition of axon outgrowth of cortical neurons required Rnd2 and down-regulation of R-Ras activity. On the other hand, Plexin-C1 displayed R-Ras GAP activity and inhibited cell migration of COS-7 cells without Rnd proteins. Therefore, R-Ras GAP activity is a common function of plexin subfamilies but the regulation of R-Ras GAP activity of plexins by Rnd proteins is different among plexin subfamilies.

    DOI: 10.1074/jbc.M805213200

    PubMed

    J-GLOBAL

  • Regulation of cell morphology and motility by Dock family proteins 査読

    Hironori Katoh

    Seikagaku   81 ( 8 )   711 - 716   2009年( ISSN:0037-1017

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  • Lysophosphatidic acid and thrombin receptors require both Gα<sup>12</sup> and Gα<sup>13</sup> to regulate axonal morphology in hippocampal neurons 査読

    J. Yamazaki, H. Katoh, M. Negishi

    Biological and Pharmaceutical Bulletin   31 ( 12 )   2216 - 2222   2008年12月( ISSN:0918-6158

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1248/bpb.31.2216

    CiNii Article

  • Dock4 Regulates Dendritic Development in Hippocampal Neurons 査読

    Shuhei Ueda, Satoshi Fujimoto, Kiyo Hiramoto, Manabu Negishi, Hironori Katoh

    JOURNAL OF NEUROSCIENCE RESEARCH   86 ( 14 )   3052 - 3061   2008年11月( ISSN:0360-4012

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Dendrite development is required for establishing proper neuronal connectivity. Rho-family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up-regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C-terminal Crk-binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. (c) 2008 Wiley-Liss, Inc.

    DOI: 10.1002/jnr.21763

    PubMed

  • Rac-GAP α-Chimerin Regulates Motor-Circuit Formation as a Key Mediator of EphrinB3/EphA4 Forward Signaling 査読

    T. Iwasato, H. Katoh, H. Nishimaru, Y. Ishikawa, H. Inoue, Y.M. Saito, R. Ando, M. Iwama, R. Takahashi, M. Negishi, S. Itohara

    Cell   130 ( 4 )   742 - 753   2007年08月( ISSN:0092-8674

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cell.2007.07.022

    J-GLOBAL

  • RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism 査読

    Nao Yamaki, Manabu Negishi, Hironori Katoh

    EXPERIMENTAL CELL RESEARCH   313 ( 13 )   2821 - 2832   2007年08月( ISSN:0014-4827

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    In normal epithelial cells, cell-matrix interaction is required for cell survival and proliferation, whereas disruption of this interaction causes epithelial cells to undergo apoptosis called anoikis. Here we show that the small GTPase RhoG plays an important role in the regulation of anoikis. HeLa cells are capable of anchorage-independent cell growth and acquire resistance to anoikis. We found that RNA interference-mediated knockdown of RhoG promoted anoikis in HeLa cells. Previous studies have shown that RhoG activates Rac1 and induces several cellular functions including promotion of cell migration through its effector ELMO and the ELMO-binding protein Dock180 that function as a Rac-specific guanine nucleotide exchange factor. However, RhoG-induced suppression of anoikis was independent of the ELMO- and Dock180-mediated activation of Rac1. On the other hand, the regulation of anoikis by RhoG required phosphatidylinositol 3-kinase (PI3K) activity, and constitutively active RhoG bound to the PI3K regulatory subunit p85 alpha and induced the PI3K-dependent phosphorylation of Akt. Taken together, these results suggest that RhoG protects cells from apoptosis caused by the loss of anchorage through a PI3K-dependent mechanism, independent of its activation of Rac1. (c) 2007 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.yexcr.2007.05.010

    PubMed

  • Interaction of arginine-rich peptides with membrane-associated proteoglycans is crucial for induction of actin organization and macropinocytosis 査読

    Ikuhiko Nakase, Akiko Tadokoro, Noriko Kawabata, Toshihide Takeuchi, Hironori Katoh, Kiyo Hiramoto, Manabu Negishi, Motoyoshi Nomizu, Yukio Sugiura, Shiroh Futaki

    BIOCHEMISTRY   46 ( 2 )   492 - 501   2007年01月( ISSN:0006-2960

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    掲載種別:研究論文(学術雑誌)  

    Arginine-rich peptides, including octaarginine (R8), HIV-1 Tat, and branched-chain arginine-rich peptides, belong to one of the major classes of cell-permeable peptides which deliver various proteins and macromolecules to cells. The importance of the endocytic pathways has recently been demonstrated in the cellular uptake of these peptides. We have previously shown that macropinocytosis is one of the major pathways for cellular uptake and that organization of the F-actin accompanies this process. In this study, using proteoglycan-deficient CHO cells, we have demonstrated that the membrane-associated proteoglycans are indispensable for the induction of the actin organization and the macropinocytic uptake of the arginine-rich peptides. We have also demonstrated that the cellular uptake of the Tat peptide is highly dependent on heparan sulfate proteoglycan (HSPG), whereas the R8 peptide uptake is less dependent on HSPG. This suggests that the structure of the peptides may determine the specificity for HSPG, and that HSPG is not the sole receptor for macropinocytosis. Comparison of the HSPG specificity of the branched-chain arginine-rich peptides in cellular uptake has suggested that the charge density of the peptides may determine the specificity. The activation of the Rac protein and organization of the actin were observed within a few minutes after the peptide treatment. These data strongly suggest the possibility that the interaction of the arginine-rich peptides with the membrane-associated proteoglycans quickly activates the intracellular signals and induces actin organization and macropinocytotis.

    DOI: 10.1021/bi0612824

    PubMed

    J-GLOBAL

  • R-Ras controls axon specification upstream of glycogen synthase kinase-3β through integrin-linked kinase 査読

    I. Oinuma, H. Katoh, M. Negishi

    Journal of Biological Chemistry   282 ( 1 )   303 - 318   2007年01月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.M607979200

    PubMed

  • Dock4 is regulated by RhoG and promotes Rac-dependent cell migration 査読

    Kiyo Hiramoto, Manabu Negishi, Hironori Katoh

    EXPERIMENTAL CELL RESEARCH   312 ( 20 )   4205 - 4216   2006年12月( ISSN:0014-4827

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Cell migration is essential for normal development and many pathological processes including tumor metastasis. Rho family GTPases play important roles in this event. In particular, Rac is required for lamellipodia formation at the leading edge during migration. Dock4 is a member of the Dock180 family proteins, and Dock4 mutations are present in a subset of human cancer cell lines. However, the function and the regulatory mechanism of Dock4 remain unclear. Here we show that Dock4 is regulated by the small GTPase RhoG and its effector ELMO and promotes cell migration by activating Rac1. Dock4 formed a complex with ELMO, and expression of active RhoG induced translocation. of the Dock4-ELMO complex from the cytoplasm to the plasma membrane and enhanced the Dock4- and ELMO-dependent Rac1 activation and cell migration. on the other hand, RNA interference-mediated knockdown of Dock4 in NIH3T3 cells reduced cell migration. Taken together, these results suggest that Dock4 plays an important role in the regulation of cell migration through activation of Rac1, and that RhoG is a key upstream regulator for Dock4. (c) 2006 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.yezcr.2006.09.006

    PubMed

    J-GLOBAL

  • Regulation of neuronal morphology by Toca-1, an F-BAR/EFC protein that induces plasma membrane invagination 査読

    Tetsuhiro Kakimoto, Hironori Katoh, Manabu Negishi

    Journal of Biological Chemistry   281 ( 39 )   29042 - 29053   2006年09月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Actin reorganization is important for regulation of neuronal morphology. Neural Wiskott-Aldrich syndrome protein (NWASP) is an important regulator of actin polymerization and also known to be strongly expressed in brain. Recently, Toca-1 (transducer of Cdc42-dependent actin assembly) has been shown to be required for Cdc42 to activate N-WASP from biochemical experiments. Toca-1 has three functional domains: an F-BAR/EFC domain at the N terminus, an HR1 at the center, and an SH3 domain at the C terminus. The F-BAR/EFC domain induces tubular invagination of plasma membrane, while Toca-1 binds both N-WASP and Cdc42 through the SH3 domain and the HR1, respectively. However, the physiological role of Toca-1 is completely unknown. Here we have investigated the neural function of Toca-1. Toca-1 is strongly expressed in neurons including hippocampal neurons in developing brain at early times. Knockdown of Toca-1 in PC12 cells significantly enhances neurite elongation. Consistently, overexpression of Toca-1 suppresses neurite elongation through the F-BAR/EFC domain with a membrane invaginating property, suggesting an implication of membrane trafficking in the neural function of Toca-1. In addition, knockdown of N-WASP, to our surprise, also enhances neurite elongation in PC12 cells, which is in clear contrast to the previous report that dominant negative mutants of N-WASP suppress neurite extension in PC12 cells. On the other hand, knockdown of Toca-1 in cultured rat hippocampal neurons enhances axon branching a little but not axon elongation, while knockdown of N-WASP enhances both axon elongation and branching. These results suggest that a vesicle trafficking regulator Toca-1 regulates different aspects of neuronal morphology from N-WASP. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

    DOI: 10.1074/jbc.M604025200

    PubMed

  • Sema4D/plexin-B1 activates GSK-3β through R-Ras GAP activity, inducing growth cone collapse 査読

    Y. Ito, I. Oinuma, H. Katoh, K. Kaibuchi, M. Negishi

    EMBO Reports   7 ( 7 )   704 - 709   2006年07月( ISSN:1469-221X

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/sj.embor.7400737

    PubMed

  • Small GTPase Rnd1 is involved in neuronal activity-dependent dendritic development in hippocampal neurons 査読

    Y Ishikawa, H Katoh, M Negishi

    NEUROSCIENCE LETTERS   400 ( 3 )   218 - 223   2006年06月( ISSN:0304-3940

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    掲載種別:研究論文(学術雑誌)  

    Rho family small GTPases are key regulators for neuronal morphogenesis including dendritogenesis. We recently have shown that Rnd1, a member of the Rho family, is highly expressed in brain during the synaptogenic stage and is involved in dendritic spine formation. However, the mechanism by which Rnd1 regulates dendritic development including spine morphogenesis remains unknown. Here we report that Rnd1, a member of the Rho family, plays a critical role in neuronal activity-dependent dendritic development in hippocampal neurons. Overexpression of Rnd1 promoted dendritic growth and branching in cultured hippocampal neurons. On the other hand, suppression of endogenous Rnd1 expression by RNA interference significantly inhibited neuronal activity-dependent dendritic development and this inhibitory effect was canceled by inhibition of RhoA effector ROCK. In addition, knockdown of Rnd1 also abolished dendritic development promoted by treatment with brain-derived neurotrophic factor in hippocampal neurons. Our findings demonstrate that Rnd1 is involved in signaling pathways of neuronal activity-dependent dendritic development. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2006.02.064

    PubMed

  • Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activity inhibits cell migration by regulating β1 integrin activity 査読

    I. Oinuma, H. Katoh, M. Negishi

    Journal of Cell Biology   173 ( 4 )   601 - 613   2006年05月( ISSN:0021-9525

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1083/jcb.200508204

    PubMed

  • Pragmin, a novel effector of Rnd2 GTPase, stimulates RhoA activity 査読

    H Tanaka, H Katoh, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   281 ( 15 )   10355 - 10364   2006年04月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    The Rho family of small GTPases has been implicated in the reorganization of actin cytoskeleton and subsequent morphological changes in various cells. Rnd2 is a member of the Rnd subfamily, comprising Rnd1, Rnd2, and Rnd3. In contrast to Rnd1 and Rnd3, displaying an antagonistic action for RhoA signaling, signaling pathways of Rnd2 are not well known. Here we have performed a yeast two-hybrid screen using Rnd2 as bait and identified a novel Rnd2 effector protein, predominantly expressed in neurons, including cortical and hippocampal neurons. We named it Pragmin (pragma of Rnd2). In in vivo and in vitro binding assays, Pragmin specifically binds to Rnd2 among the Rho family GTPases in a GTP-dependent manner. Rnd2-bound Pragmin significantly stimulates RhoA activity and induces cell contraction through RhoA and the Rho-kinase pathway in HeLa cells. In PC12 cells, expressing Pragmin inhibits nerve growth factor-induced neurite outgrowth in response to Rnd2, and knock-down of Pragmin by Pragmin-specific small interfering RNA enhances neurite elongation. Therefore, Rnd2 regulates neurite outgrowth by functioning as the RhoA activator through Pragmin, in contrast to Rnd1 and Rnd3 inhibiting RhoA signaling.

    DOI: 10.1074/jbc.M511314200

    PubMed

  • Differential distribution of ELMO1 and ELMO2 mRNAs in the developing mouse brain 査読

    H Katoh, S Fujimoto, C Ishida, Y Ishikawa, M Negishi

    BRAIN RESEARCH   1073   103 - 108   2006年02月( ISSN:0006-8993

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    ELMO is an upstream regulator of the Rho family small GTPase Rac. We investigated the distributions of mRNAs of two subtypes of ELMO, ELMO1 and ELMO2, in the developing mouse brain. Both ELMO1 and ELMO2 mRNAs are widely distributed in the developing mouse brain, but they were expressed in different neuronal populations in the cerebral cortex, thalamus, and cerebellum. Thus, ELMO1 and ELMO2 may play different roles during brain development. (c) 2005 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2005.12.085

    PubMed

  • In vivo function of Rnd2 in the development of neocortical pyramidal neurons 査読

    K Nakamura, Y Yamashita, N Tamamaki, H Katoh, T Kaneko, M Negishi

    NEUROSCIENCE RESEARCH   54 ( 2 )   149 - 153   2006年02月( ISSN:0168-0102

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    掲載種別:研究論文(学術雑誌)  

    The present study examined the in vivo role of Rnd2, a Rho family small GTPase, in brain development. Rnd2 was expressed by radially migrating cells, which primarily develop to pyramidal neurons, during their stay in the subventricular zone of embryonic cerebral cortex and hippocampus. Exogenous expression of wild-type and a constitutively active Rnd2, but not a negative mutant of Rnd2, in radially migrating cells by in utero electroporation disturbed their morphology and migration to upper layers. These results indicate that Rnd2 functions in vivo as a regulator of the migration and morphological changes associated with the development of pyramidal neurons. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2005.10.008

    PubMed

    CiNii Article

    J-GLOBAL

  • Activation of Rac1 by RhoG regulates cell migration 査読

    H Katoh, K Hiramoto, M Negishi

    JOURNAL OF CELL SCIENCE   119 ( 1 )   56 - 65   2006年01月( ISSN:0021-9533

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Cell migration is essential for normal development and many pathological processes. Rho-family small GTPases play important roles in this event. In particular, Rac regulates lamellipodia formation at the leading edge during migration. The small GTPase RhoG activates Rac through its effector ELMO and the ELMO-binding protein Dock180, which functions as a Rac-specific guanine nucleotide exchange factor. Here we investigated the role of RhoG in cell migration. RNA interference-mediated knockdown of RhoG in HeLa cells reduced cell migration in Transwell and scratch-wound migration assays. In RhoG-knockdown cells, activation of Rac1 and formation of lamellipodia at the leading edge in response to wounding were attenuated. By contrast, expression of active RhoG promoted cell migration through ELMO and Dock180. However, the interaction of Dock180 with Crk was dispensable for the activation of Rac1 and promotion of cell migration by RhoG. Taken together, these results suggest that RhoG contributes to the regulation of Rac activity in migrating cells.

    DOI: 10.1242/jcs.02720

    PubMed

  • GEFs and gaps of Rho family GTPases 査読

    M. Negishi, H. Katoh

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.   51 ( 6 Suppl )   693 - 698   2006年

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  • R-Ras as a key player for signaling pathway of plexins 査読

    M Negishi, Oinuma, I, H Katoh

    MOLECULAR NEUROBIOLOGY   32 ( 3 )   217 - 222   2005年12月( ISSN:0893-7648

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    掲載種別:研究論文(学術雑誌)  

    Axon guidance represents an important step in the formation of neuronal networks. Axons are guided by various guidance factors, such as semaphorins, slits, ephrins, and netrins. Plexins are cell surface receptors for the repulsive molecules of the semaphorin family. Cytoplasmic regions of plexins are responsible for initiating cellular signal transduction, resulting in axon repulsion. Recent advances have shed light on the signal transduction mechanism of plexins and the mechanisms by which it leads to a repulsive response. Plexin-B1 possesses an intrinsic guanine triphosphate (GTP)ase activating protein activity for R-Ras, a member of Ras family of small GTPases that has been implicated in promoting cell adhesion and neurite outgrowth through integrin activation. Stimulation of Plexin-B1 by Sema4D induces collapse of the growth cone through down-regulation of R-Ras activity. This article summarizes current understanding of the signaling mechanisms of plexins.

    DOI: 10.1385/MN:32:3:217

    PubMed

  • Socius, a novel binding partner of Gア12/13, promotes the Gア12-induced RhoA activation. 査読

    Tateiwa, K, Katoh, H, Negishi, M

    Biochem. Biophys. Res. Commun.,337, 615-620   337 ( 2 )   615 - 620   2005年11月( ISSN:0006-291X

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbrc.2005.09.097

  • Two G12 family G proteins, Gア12 and Gア13, show different subcellular localization. 査読

    Yamazaki, J, Katoh, H, Yamaguchi, Y, Negishi, M

    Biochem. Biophys. Res. Commun.,332, 782-786   332 ( 3 )   782 - 786   2005年07月( ISSN:0006-291X

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbrc.2005.05.023

  • Plexins: axon guidance and signal transduction 査読

    M Negishi, Oinuma, I, H Katoh

    CELLULAR AND MOLECULAR LIFE SCIENCES   62 ( 12 )   1363 - 1371   2005年06月( ISSN:1420-682X

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    Axon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as semaphorins, ephrins and netrin. Plexins function as receptors for the repulsive axonal guidance molecules semaphorins. Intracellular domains of plexins are responsible for initiating cellular signal transduction inducing axon repulsion. Recent advances have revealed molecular mechanisms for plexin-mediated cytoskeletal reorganization, leading to repulsive responses, and small GTPases play important roles in this signaling. Plexin-B1 activates Rho through Rho-specific guanine nucleotide exchange factors, leading to neurite retraction. Plexin-B1 possesses an intrinsic GTPase-activating protein activity for R-Ras and induces growth cone collapse through R-Ras inactivation. In this review we survey current understanding of the signaling mechanisms of plexins.

    DOI: 10.1007/s00018-005-5018-2

    PubMed

  • Rho family GTPases and dendrite plasticity 査読

    M Negishi, H Katoh

    NEUROSCIENTIST   11 ( 3 )   187 - 191   2005年06月( ISSN:1073-8584

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    掲載種別:研究論文(学術雑誌)  

    Dendrite structures exert a profound influence on neuronal information processing. The Rho family GTPases have been implicated in the regulation of dendritic development. Among them, Rho, Rac, and Cdc42 have been characterized extensively, and Rac and Cdc42 promote dendrite growth and branching, whereas Rho acts as a negative regulator for dendrite growth. Recently, other members of Rho family GTPases, including Rnd1 and Rnd2, have also been shown to be involved in the regulation of dendrite development. Rnd1 promotes spine maturation, and Rnd2 stimulates dendrite branching through its specific effector, Rapostlin. Thus, a variety of Rho family GTPases play important roles in dendritic development.

    DOI: 10.1177/1073858404268768

    PubMed

  • Rho family GTPases and dendrite plasticity 査読

    Manabu Negishi, Hironori Katoh

    Neuroscientist   11 ( 3 )   187 - 191   2005年06月( ISSN:1073-8584

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    Dendrite structures exert a profound influence on neuronal information processing. The Rho family GTPases have been implicated in the regulation of dendritic development. Among them, Rho, Rac, and Cdc42 have been characterized extensively, and Rac and Cdc42 promote dendrite growth and branching, whereas Rho acts as a negative regulator for dendrite growth. Recently, other members of Rho family GTPases, including Rnd1 and Rnd2, have also been shown to be involved in the regulation of dendrite development. Rnd1 promotes spine maturation, and Rnd2 stimulates dendrite branching through its specific effector, Rapostlin. Thus, a variety of Rho family GTPases play important roles in dendritic development. Copyright © 2005 Sage Publications.

    DOI: 10.1177/1073858404268768

    PubMed

  • Direct interaction of Rnd1 with FRS2β regulates Rnd1-induced down-regulation of RhoA activity and is involved in fibroblast growth factor-induced neurite outgrowth in PC12 cells 査読

    A. Harada, H. Katoh, M. Negishi

    Journal of Biological Chemistry   280 ( 18 )   18418 - 18424   2005年05月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.M411356200

    PubMed

    J-GLOBAL

  • Signaling mechanisms of axon guidance factor, semaphorins 査読

    M. Negishi, H. Katoh

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   50 ( 2 )   141 - 147   2005年

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  • Molecular dissection of the semaphorin 4D receptor Plexin-B1-stimulated R-Ras GTPase-activating protein activity and neurite remodeling in hippocampal neurons 査読

    Oinuma, I, H Katoh, M Negishi

    JOURNAL OF NEUROSCIENCE   24 ( 50 )   11473 - 11480   2004年12月( ISSN:0270-6474

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    掲載種別:研究論文(学術雑誌)  

    Plexins serve as receptors for repulsive axonal guidance molecules semaphorins. The cytoplasmic domain of the semaphorin 4D (Sema4D) receptor, Plexin-B1 has two separated Ras GTPase-activating protein (GAP)-homologous domains, C1 and C2. Recently, we reported that the Rho family small GTPase Rnd1 associates with Plexin-B1, and the Plexin-B1-Rnd1 complex stimulates GTPase activity of R-Ras, inducing growth cone collapse in hippocampal neurons in response to Sema4D. However, the molecular mechanisms by which Plexin-B1 exhibits the GAP activity remain unclear. In this report, critical roles of Rnd1 and Sema4D in Plexin-B1-stimulated R-Ras GAP activity and neurite remodeling were examined. The N-terminal region of the cytoplasmic domain of Plexin-B1 containing the C1 domain interacts with the C-terminal region containing the C2 domain, and Rnd1 disrupts this interaction. On the other hand, Sema4D induces clustering of Rnd1-bound Plexin-B1, in parallel with inactivation of R-Ras in cells. Antibody clustering of the recombinant cytoplasmic domain of Plexin-B1 in the presence of Rnd1 triggers the R-Ras GAP activity. Deletion of the extracellular domain of Plexin-B1 causes ligand-independent clustering of the receptor, rendering the receptor constitutively active in the presence of Rnd1, and induces contraction of COS-7 cells and inhibition of neurite outgrowth in hippocampal neurons. These results indicate that Rnd1 opens the two R-Ras GAP domains of Plexin-B1, and Sema4D-induced receptor clustering stimulates R-Ras GAP activity and neurite remodeling in hippocampal neurons.

    DOI: 10.1523/JNEUROSCI.3257-04.2004

    PubMed

  • The semaphorin 4D receptor plexin-B1 is a GTPase activating protein for R-Ras 査読

    Oinuma, I, Y Ishikawa, H Katoh, M Negishi

    SCIENCE   305 ( 5685 )   862 - 865   2004年08月( ISSN:0036-8075

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    掲載種別:研究論文(学術雑誌)  

    Plexins are cell surface receptors for semaphorin molecules, and their interaction governs cell adhesion and migration in a variety of tissues. We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates the intrinsic guanosine triphosphatase ( GTPase) activity of R-Ras, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of Plexin-B1 with Rnd1, a small GTP-binding protein of the Rho family. Down-regulation of R-Ras activity by the Plexin-B1-Rnd1 complex was essential for the Sema4D-induced growth cone collapse in hippocampal neurons. Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras.

    DOI: 10.1126/science.1097545

    PubMed

  • Identification of splicing variants of rapostlin, a novel Rnd2 effector that interacts with neural Wiskott-Aldrich syndrome protein and induces neurite branching 査読

    T Kakimoto, H Katoh, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 14 )   14104 - 14110   2004年04月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Rho family GTPases regulate neuronal morphology. Rnd subfamily is a new branch of Rho family GTPases. Of these GTPases, Rnd2 is specifically expressed in brain. We recently identified Rapostlin as a novel effector of Rnd2. Rapostlin induces neurite branching in response to Rnd2 in PC12 cells. During the cloning of Rapostlin, we have found two mainly expressed splicing variants of Rapostlin (renamed as RapostlinL), Rapost-linM and RapostlinS, lacking 29 residues and 61 residues within the unique insert region at the center, respectively, and three minor variants, RapostlinLd, RapostlinMd, and RapostlinSd, each with the identical five-amino acid deletion from RapostlinL, RapostlinM, and RapostlinS, respectively. RapostlinL is predominantly expressed in brain, whereas RapostlinS is expressed ubiquitously. In a dot-blot assay, all splicing variants bind to Rnd2 in a GTP-dependent manner. However, RapostlinM and RapostlinS induce less neurite branching when coexpressed with Rnd2 in PC12 cells, indicating that the insert region is important for the branching activity of RapostlinL. All splicing variants bind to N-WASP in vitro and in vivo through the SH3 domain at the carboxyl terminus, and the SH3 domain is essential for branching activity of RapostlinL. In immunoprecipitation experiments, Rnd2 reduces Ra-postlinL-N-WASP interaction, whereas it has little effect on the interaction of RapostlinM or RapostlinS with N-WASP. Therefore, we found that functionally different splicing variants of Rapostlin have different responses to Rnd2 in association with N-WASP.

    DOI: 10.1074/jbc.M312763200

    PubMed

    J-GLOBAL

  • PACAP activates Rac1 and synergizes with NGF to activate ERK1/2, thereby inducing neurite outgrowth in PC12 cells 査読

    Y Sakai, H Hashimoto, N Shintani, H Katoh, M Negishi, C Kawaguchi, A Kasai, A Baba

    MOLECULAR BRAIN RESEARCH   123 ( 1-2 )   18 - 26   2004年04月( ISSN:0169-328X

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    掲載種別:研究論文(学術雑誌)  

    The mechanisms linked to the neuritogenic effect of PACAP acting in synergy with NGF were analyzed in PC 12 cells. Recently, we have shown that PACAP synergizes with NGF to stimulate PACAP gene transcription and neurite outgrowth, differentially dependent on both the ERK1/2 and p38 MAP kinase pathways in PC12 cells. This suggests that PACAP modulates mitogen signaling pathways governing cell differentiation, in part through MAP kinase activation and an autocrine mechanism. Here, we studied the mechanism of the underlying neuritogenic actions of PACAP. PACAP induced transient activation of Rac1, a small GTPase involved in neurite outgrowth, in a P13-kinase-independent manner, and stimulated accumulation of active Rac1 at filamentous actin-rich protrusions on the cell surface to induce subsequent neurite formation. PACAP had no additional effect on the activity of Rac1 beyond the effect of NGF and failed to activate Ras or Cdc42. By contrast, simultaneous treatment with PACAP and NGF acts in synergy to induce prolonged activation of ERK1/2. These results indicate for the first time that PACAP induces activation of Rac1 associated with neurite outgrowth and suggest that the synergistic effect of PACAP and NGF on neurite extension is due to enhanced activation of ERK1/2. (C) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.molbrainres.2003.12.013

  • Rho family GTPases as key regulators for neuronal network formation 査読

    M. Negishi, H. Katoh

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   49 ( 3 Suppl )   331 - 336   2004年

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  • A role of Rnd1 GTPase in dendritic spine formation in hippocampal neurons 査読

    Y Ishikawa, H Katoh, M Negishi

    JOURNAL OF NEUROSCIENCE   23 ( 35 )   11065 - 11072   2003年12月( ISSN:0270-6474

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    掲載種別:研究論文(学術雑誌)  

    Rho family of small GTPases are key regulators for morphological changes of neurons on the basis of reorganization of the actin cytoskeleton. Rnd1, a novel member of this family, is predominantly expressed in neurons in brain; however, the neuronal functions of Rnd1 are not known. Here we investigated the effect of Rnd1 on neuronal morphology. Northern blot analysis of Rnd1 expression in rat brain showed that Rnd1 mRNA was highly expressed during early postnatal period, the synaptogenic stage. In situ hybridization analysis at this period revealed that Rnd1 mRNA was strongly expressed in neurons, including the hippocampal pyramidal neurons. Furthermore, immunoblot analysis showed that Rnd1 protein was localized in synaptosomal membrane fraction. Ectopical overexpression of Rnd1 in cultured rat hippocampal neurons promoted the elongation of dendritic spines. On the other hand, suppression of endogenous Rnd1 level by antisense oligonucleotide of Rnd1 caused the increase in the percentage of headless protrusions accompanied by the reduction in the spine number and spine width and shortened the length of the headless protrusions. These results indicate that Rnd1 plays a role in spine formation in the developmental synaptogenic stage.

    PubMed

  • Direct interaction of Rnd1 with plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by plexin-B1 and induces cell contraction in COS-7 cells 査読

    Oinuma, I, H Katoh, A Harada, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 28 )   25671 - 25677   2003年07月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Plexins are receptors for the axon guidance molecule semaphorins, and several lines of evidence suggest that Rho family small GTPases are implicated in the downstream signaling of Plexins. Recent studies have demonstrated that Plexin-B1 activates RhoA and induces growth cone collapse through Rho-specific guanine nucleotide exchange factor PDZ-RhoGEF. Here we show that Rnd1, a member of Rho family GTPases, directly interacted with the cytoplasmic domain of Plexin-B1. In COS-7 cells, coexpression of Rnd1 and Plexin-B1 induced cell contraction in response to semaphorin 4D (Sema4D), a ligand for Plexin-B1, whereas expression of Plexin-B1 alone or coexpression of Rnd1 and a Rnd1 interaction-defective mutant of Plexin-B1 did not. The Sema4D-induced contraction in Plexin-B1/Rnd1-expressing COS-7 cells was suppressed by dominant negative RhoA, a Rho-associated kinase inhibitor, a dominant negative form of PDZ-RhoGEF, or deletion of the carboxyl-terminal PDZ-RhoGEF-binding region of Plexin-B1, indicating that the PDZ-RhoGEF/RhoA/Rho-associated kinase pathway is involved in this morphological effect. We also found that Rnd1 promoted the interaction between Plexin-B1 and PDZ-RhoGEF and thereby dramatically potentiated the Plexin-B1-mediated RhoA activation. We propose that Rnd1 plays an important role in the regulation of Plexin-B1 signaling, leading to Rho activation during axon guidance and cell migration.

    DOI: 10.1074/jbc.M303047200

    PubMed

    J-GLOBAL

  • RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo 査読

    H Katoh, M Negishi

    NATURE   424 ( 6947 )   461 - 464   2003年07月( ISSN:0028-0836

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    The small GTPase Rac has a central role in regulating the actin cytoskeleton during cell migration and axon guidance(1). Elmo has been identified as an upstream regulator of Rac1 that binds to and functionally cooperates with Dock180 (refs 2-4). Dock180 does not contain a conventional catalytic domain for guanine nucleotide exchange on Rac, but possesses a domain that directly binds to and specifically activates Rac1 (refs 5, 6). The small GTPase RhoG mediates several cellular morphological processes, such as neurite outgrowth in neuronal cells, through a signalling cascade that activates Rac1 (refs 7-12); however, the downstream target of RhoG and the mechanism by which RhoG regulates Rac1 activity remain unclear. Here we show that RhoG interacts directly with Elmo in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1. The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor. We conclude that RhoG activates Rac1 through Elmo and Dock180 to control cell morphology.

    DOI: 10.1038/nature01817

    PubMed

  • N-terminal short sequences of α subunits of the G<sub>12</sub> family determine selective coupling to receptors 査読

    Y. Yamaguchi, H. Katoh, M. Negishi

    Journal of Biological Chemistry   278 ( 17 )   14936 - 14939   2003年04月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.M301409200

    PubMed

  • Rapostlin is a novel effector of Rnd2 GTPase inducing neurite branching 査読

    H Fujita, H Katoh, Y Ishikawa, K Mori, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 47 )   45428 - 45434   2002年11月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Rho family GTPases are central regulators of neuronal morphology. Recently, Rnd proteins, Rnd1, Rnd2, and Rnd3/RhoE, have been identified as new members of Rho family GTPases. Of these, Rnd2 is specifically expressed in neurons in brain; however, the signaling pathways of RnA2 are not known. Here we have performed a yeast two-hybrid screen using Rnd2 as a bait and identified a novel Rnd2-effector protein, expressed predominantly in brain. We named it Rapostlin (apostle of Rnd2). Rapostlin has two functional domains, Fer-CIP4 homology (FCH) domain at the amino terminus and SH3 (Src homology 3) domain at the carboxyl terminus. In in vitro binding assays, Rapostlin specifically binds to Rnd2 among the Rho family GTPases in a GTP-dependent manner, and the Rnd2-binding domain of Rapostlin is localized between FCH and SH3 domains. Rapostlin directly binds to microtubules, and the aminoterminal region containing the FCH domain of Rapostlin is essential for this interaction. In PC 12 cells, Rapostlin induces neurite branching in response to Rnd2, and at least the amino-terminal region of Rapostlin is necessary for this activity. Therefore, Rapostlin is the first effector of RnA2, regulating neurite branch formation.

    DOI: 10.1074/jbc.M208090200

    PubMed

  • Developmental changes in expression of small GTPase RhoG mRNA in the rat brain 査読

    Y Ishikawa, H Katoh, K Nakamura, K Mori, M Negishi

    MOLECULAR BRAIN RESEARCH   106 ( 1-2 )   145 - 150   2002年10月( ISSN:0169-328X

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    掲載種別:研究論文(学術雑誌)  

    We have recently reported that RhoG, a member of Rho family small GTPases, is involved in neurite outgrowth in cultured neuronal cells. Here, we report the expression of RhoG mRNA in the developing rat brain by in situ hybridization analysis. At embryonic day 16, RhoG expression was observed throughout the ventricular zone, but was down-regulated in the region at birth. On the other hand, RhoG expression at postnatal day 20 was highly enriched in white matter tracts, including the corpus callosum, the anterior commissure, and the cerebellar white matter, and double-labeling experiments demonstrated that major RhoG-expressing cells in white matter tracts were oligodendrocytes. These results suggest distinct pre- and postnatal roles of RhoG in the development of the central nervous system. (C) 2002 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0169-328X(02)00413-8

    PubMed

  • Cyclopentenone prostaglandin receptors 査読

    M Negishi, H Katoh

    PROSTAGLANDINS & OTHER LIPID MEDIATORS   68-9   611 - 617   2002年08月( ISSN:0090-6980

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    掲載種別:研究論文(学術雑誌)  

    Cyclopentenone prostaglandins.(PGs), such as 15-deoxy-12,13-didehydro-14,15-didehydro-PGJ(2) (15d-Delta(12,14)-PGJ(2)), 12,13-didehydro-PGJ(2) (Delta(12)-PGJ(2)) and PGA(2), are actively transported into cells and promote the expression of a variety of genes. The ultimate metabolite of PGD(2), 15d-Delta(12,14)- PGJ(2), specifically binds to a nuclear receptor, they isoform of the peroxisome proliferator-activated receptor, thereby promoting adipogenesis. Cyclopentenone PGs also induce the expression of various stress genes, such as heat shock proteins (HSPs), the immunoglobulin heavy chain binding protein (BiP) and protein disulfide isomerase by acting through heat shock element or unfolded protein response element. Overall, cyclopentenone PGs regulate cell growth, cell differentiation and stress responses by regulating various gene expression. (C) 2002 Elsevier Science Inc. All rights reserved.

    DOI: 10.1016/S0090-6980(02)00059-X

    PubMed

  • Rho family GTPases as key regulators for neuronal network formation 査読

    M Negishi, H Katoh

    JOURNAL OF BIOCHEMISTRY   132 ( 2 )   157 - 166   2002年08月( ISSN:0021-924X

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    Rho family GTPases act as transducers of signals from extracellular stimuli to the cytoskeleton and gene expression. Their actions are temporal and spatial determinants for cellular functions. The cellular functions of Rho family GTPases have been studied in fibroblasts and endothelial cells, and recent advances have revealed their roles in the regulation of neuronal network formation, including migration, neurite outgrowth, polarity, axon guidance, dendrite maturation and synapse formation. In addition, a significant number of X-linked mental retardation genes have been shown to encode components directly involved in signal transduction pathways of Rho family GTPases, underscoring the view that Rho family GTPases essentially participate in the neuronal network formation. In this review, we will overview current understanding of the functions of Rho family GTPases in neuronal network formation.

    PubMed

    CiNii Article

  • Gα<sub>12</sub> and Gα<sub>13</sub> interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity 査読

    Y. Yamaguchi, H. Katoh, K. Mori, M. Negishi

    Current Biology   12 ( 15 )   1353 - 1358   2002年08月( ISSN:0960-9822

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/S0960-9822(02)01034-5

    PubMed

  • Vps4-A (vacuolar protein sorting 4-A) is a binding partner for a novel Rho family GTPase, Rnd2 査読

    H Tanaka, H Fujita, H Katoh, K Mori, M Negishi

    BIOCHEMICAL JOURNAL   365 ( 2 )   349 - 353   2002年07月( ISSN:0264-6021

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    掲載種別:研究論文(学術雑誌)  

    Rho family GTPases are implicated in a variety of biological activities, including endocytic vesicle trafficking. Rnd2 is a new member of Rho family GTPases, but its biological functions are not known. In the present study, we have performed a yeast two-hybrid screening using Rnd2 as bait and revealed that Rnd2 binds specifically to Vps4-A (where Vsp4-A is vacuolar protein sorting 4-A), a member of the AAA ATPase family and a central regulator for early endosome trafficking. This interaction was determined by the yeast two-hybrid system, in vitro binding and co-immunoprecipitation studies. Vps4-A associated with both guanosine 5'-[beta-thio]triphosphate-bound active and guanosine 5'-[beta-thio]diphosphate-bound inactive forms of Rnd2. An ATPase-defective Vps4-A mutant, Vps4-A(E228Q), expressed in HeLa cells was accumulated in the early endosomes. When Rnd2 was co-expressed with Vps4-A(E228Q), Rnd2 was recruited to the Vps4-A-bound early endosomes. These results suggest that Rnd2 is involved in the regulation of endosomal trafficking via direct binding to Vps4-A.

    DOI: 10.1042/BJ20020062

    PubMed

  • The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area 査読

    K Nakamura, K Matsumura, T Kaneko, S Kobayashi, H Katoh, M Negishi

    JOURNAL OF NEUROSCIENCE   22 ( 11 )   4600 - 4610   2002年06月( ISSN:0270-6474

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    掲載種別:研究論文(学術雑誌)  

    Fever is the widely known hallmark of disease and is induced by the action of the nervous system. It is generally accepted that prostaglandin (PG) E-2 is produced in response to immune signals and then acts on the preoptic area (POA), which triggers the stimulation of the sympathetic system, resulting in the production of fever. Actually, the EP3 subtype of PGE receptor, which is essential for the induction of fever, is known to be localized in POA neurons. However, the neural pathway mediating the pyrogenic transmission from the POA to the sympathetic system remains unknown. To identify the neuronal groups involved in the fever-inducing pathway, we first investigated Fos expression in medullary regions of rats after central administrations of PGE(2). PGE(2) application to the lateral ventricle or directly to the POA strikingly increased the number of Fos-positive neurons in the rostral part of the raphe pallidus nucleus (rRPa). Most of these neurons did not exhibit serotonin immunoreactivity. Microinjection of muscimol, a GABA(A) receptor agonist, into the rRPa blocked fever and thermogenesis in brown adipose tissue induced by intra-POA as well as by intracerebroventricular PGE(2) applications. Furthermore, neural tract tracing studies revealed a direct projection from EP3 receptor-expressing POA neurons to the rRPa. Our results demonstrate that the rRPa, which has never been associated with the fever mechanism, mediates the pyrogenic neurotransmission from the POA to the peripheral sympathetic effectors contributing to fever development.

  • Regulation of neurite formation by Rho family GTPases 査読

    M Negishi, H Katoh

    SEIKAGAKU   74 ( 5 )   395 - 398   2002年05月( ISSN:0037-1017

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    掲載種別:研究論文(学術雑誌)  

    PubMed

  • Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers 査読

    H Katoh, A Harada, K Mori, M Negishi

    MOLECULAR AND CELLULAR BIOLOGY   22 ( 9 )   2952 - 2964   2002年05月( ISSN:0270-7306

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)  

    Rho family small GTPases are key regulators of the actin cytoskeleton in various cell types. The Rnd proteins, Rnd1, Rnd2, and Rnd3/RhoE, have been recently identified as new members of the Rho family of GTPases, and expression of Rnd1 or Rnd3 in fibroblasts causes the disassembly of actin stress fibers and the retraction of the cell body to produce extensively branching cellular processes. Here we have performed a yeast two-hybrid screening by using Rndl as bait and identified a novel protein that specifically binds to Rnd GTPases. We named this protein Socius. Socius directly binds to Rnd GTPases through its COOH-terminal region. When transfected into COS-7 cells, Socius is translocated to the cell periphery in response to Rndl and Rnd3 and colocalized with the GTPases. While expression of wild-type Socius in Swiss 3T3 fibroblasts has little effect on the actin cytoskeleton, the expression of a membrane-targeted form of Socius, containing a COOH-terminal farnesylation motif (Socius-CAAX), induces a dramatic loss of stress fibers. The inhibitory effect of Socius-CAAX on stress fiber formation is enhanced by truncation of its NH2 terminus. On the other hand, the expression of Socius-CAAX or its NH2 terminus-truncated form suppresses the Rnd-induced retraction of the cell body and the production of extensively branching cellular processes, although the disassembly of stress fibers is observed. We propose that Socius participates in the Rnd GTPase-induced signal transduction pathways, leading to reorganization of the actin cytoskeleton.

    DOI: 10.1128/MCB.22.9.2952-2964.2002

    PubMed

    J-GLOBAL

  • RhoA inhibits the nerve growth factor-induced Rac1 activation through Rho-associated kinase-dependent pathway 査読

    Y Yamaguchi, H Katoh, H Yasui, K Mori, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 22 )   18977 - 18983   2001年06月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    The Rho family of small GTPases has been shown to be involved in the regulation of neuronal morphology, and Rac and Rho exert antagonistic actions in neurite formation. In this study, we have examined the cross-talk between Rac and Rho in relation to the nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. NGF induced a rapid activation of Pac 1 and suppression of RhoA activity. Constitutively active RhoA, RhoA(V14) or constitutively active G alpha (12)-induced endogenous RhoA activation inhibited the NGF-induced Rad activation without any effect on the NGF-induced extracellular signal-regulated kinase activation. Moreover, Y-27632, an inhibitor of Rho-associated kinase, completely abolished the RhoA-induced down-regulation of the NGF-induced Rad activation. We also revealed that NGF induced a rapid recruitment of Rad to the cell surface protrusion sites and formed filamentous actin-rich protrusions. Activation of RhoA and Rho-associated kinase formed a thick ringlike structure of cortical actin filaments at the cell periphery and then inhibited the NGF-induced recruitment of Rad to protrusions. These results indicate that RhoA down-regulates the NGF-induced Rad activation through Rho-associated kinase, inhibiting the neurite formation.

    DOI: 10.1074/jbc.M100254200

    PubMed

    J-GLOBAL

  • Differential responses to nerve growth factor and epidermal growth factor in neurite outgrowth of PC12 cells are determined by Rac1 activation systems 査読

    H Yasui, H Katoh, Y Yamaguchi, J Aoki, H Fujita, K Mori, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 18 )   15298 - 15305   2001年05月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Neurite outgrowth of PC12 cells is induced by nerve growth factor (NGF) but not by epidermal growth factor (EGF). This differential response has been explained by the duration of mitogen-activated protein kinase (MAPK) activation; NGF induces sustained MAPK activation but EGF leads short-lived activation. However, precise mechanisms have not yet been understood. Here we demonstrate the difference between NGF and EGF in regulation of Rad, a small GTPase involved in neurite outgrowth, in PC12 cells. NGF phosphoinositide 3-kinase dependently induces transient activation of Rad and accumulation of active Rad at protrusion sites on the cell surface, inducing filamentous actin-rich protrusions and subsequent neurite formation in a Rac1-dependent manner. On the other hand, EGF phosphoinositide 3-kinase independently induces more transient Rad activation but neither accumulates active Rad nor forms Rac1- and filamentous actin-rich protrusions. Difference in the Rad localization between NGF and EGF was also observed with the localization of exogenously expressed green fluorescent protein-tagged Rad. The Rad-mediated protrusion by NGF is independent of MAPK cascade, but the subsequent neurite extension requires the cascade. Thus, the differential activation of Rad and localization of active Rad contribute to the difference in the ability of NGF and EGF to induce neurite outgrowth, and we propose that the MAPK cascade independent prompt activation of Rad and recruitment of active Rad at the protrusion sites trigger the initiation of neurite formation.

    DOI: 10.1074/jbc.M008546200

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  • Prostaglandin EP3 receptor protein in serotonin and catecholamine cell groups: A double immunofluorescence study in the rat brain 査読

    K Nakamura, YQ Li, T Kaneko, H Katoh, M Negishi

    NEUROSCIENCE   103 ( 3 )   763 - 775   2001年( ISSN:0306-4522

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    掲載種別:研究論文(学術雑誌)  

    Prostaglandin E-2 exerts diverse physiological actions in the central nervous system with unknown mechanisms. We have reported the immunohistochemical localization of the EP3 receptor, one of the prostaglandin E receptor subtypes, in various brain regions including many monoaminergic nuclei. In the present study, a double immunofluorescence technique with an antibody to EP3 receptor and antibodies to markers for monoamine neurons was employed to examine the expression of the receptor in serotonin and catecholamine neurons, and to reveal the distribution of the receptor-expressing monoamine neurons in the rat brain. Almost all serotonergic cells in the medulla oblongata (B1-B4) exhibited EP3 receptorlike immunoreactivity, whereas mesencephalic and pontine serotonergic cell groups (B5-B9) contained relatively small populations of EP3 receptor-immunoreactive cells. In the catecholaminergic cell groups, many of the noradrenergic A7 cells in the subcoeruleus nucleus showed immunoreactivity for the receptor. The locus coeruleus exhibited EP3 receptor-like immunoreactivity densely in the neuropil and occasionally in neuronal cell bodies, all of which were immunopositive for dopamine beta -hydroxylase, as observed by confocal laser microscopy. Many of the other noradrenergic and adrenergic cell groups contained small populations of EP3 receptor-like immunoreactive cells. In contrast, no EP3 receptor-like immuno reactivity was detected in the noradrenergic A2 and A4, the adrenergic C2, and all the dopaminergic cell groups.
    The expression of EP3 receptor by most of the serotonergic, noradrenergic and adrenergic cell groups suggests that prostaglandin E2 modulates many physiological processes mediated by widely distributed monoaminergic projections through activation of the EP3 receptor on the monoaminergic neurons; for instance, it may modulate nociceptive and autonomic processes by affecting the descending serotonergic pathway from the raphe magnus nucleus to the spinal cord. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0306-4522(01)00027-6

    PubMed

  • Rnd1, a novel Rho family GTPase, induces the formation of neuritic processes in PC12 cells 査読

    J Aoki, H Katoh, K Mori, M Negishi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   278 ( 3 )   604 - 608   2000年11月( ISSN:0006-291X

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    掲載種別:研究論文(学術雑誌)  

    Rho family GTPases have been shown to be involved in the regulation of neuronal cell morphology, including neurite extension and retraction. Rho activation leads to neurite retraction and cell rounding, whereas Rac and Cdc42 are implicated in the promotion of filopodia and lamellipodia formation in growth cones and, therefore, in neurite extension. In this study, we examined the morphological role of Rnd1, a new member of Rho family GTPases, in PC12 cells, and found that expression of Rnd1 by itself caused the formation of many neuritic processes from the cell body with disruption of the cortical actin filaments, the processes having microtubules but few filamentous actin and neurofilaments. Treatment with cytochalasin D, an inhibitor of actin polymerization, could mimic the effects of expression of Rnd1, in that this inhibitor disrupted the cortical actin filaments and induced the formation of many thin processes containing microtubules. The process formation induced by Rnd1 was inhibited by dominant negative Rad. These results suggest that Rnd1 induces the Rac-dependent neuritic process formation in part by disruption of the cortical actin filaments. (C) 2000 Academic Press.

    DOI: 10.1006/bbrc.2000.3842

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  • Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells 査読

    H Katoh, H Yasui, Y Yamaguchi, J Aoki, H Fujita, K Mori, M Negishi

    MOLECULAR AND CELLULAR BIOLOGY   20 ( 19 )   7378 - 7387   2000年10月( ISSN:0270-7306

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    掲載種別:研究論文(学術雑誌)  

    The Rho family of small GTPases has been implicated in cytoskeletal reorganization and subsequent morphological changes in various cell types. Among them, Rac and Cdc42 have been shown to be involved in neurite outgrowth in neuronal cells. In this study, we examined the role of RhoG, another member of Rho family GTPases, in nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Expression of wild-type RhoG in PC12 cells induced neurite outgrowth in the absence of NGF, and the morphology of wild-type RhoG-expressing cells was similar to that of NGF-differentiated cells. Constitutively active RhoG-transfected cells extended short neurites but developed large lamellipodial or filopodial structures at the tips of neurites. RhoG-induced neurite outgrowth was inhibited by coexpression with dominant-negative Rac1 or Cdc42. In addition expression of constitutively active RhoG elevated endogenous Rac1 and Cdc42 activities. We also found that the NGF-induced neurite outgrowth was enhanced by expression of wild-type RhoG whereas expression of dominant-negative RhoG suppressed the neurite outgrow th. Furthermore, constitutively active pas-induced neurite outgrowth was also suppressed by dominant-negative RhoG. Taken together, these results suggest that RhoG is a key regulator in NGF-induced neurite outgrowth, acting downstream of Ras and upstream of Rac1 and Cdc42 in PC12 cells.

    DOI: 10.1128/MCB.20.19.7378-7387.2000

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  • Receptor isoform-specific interaction of prostaglandin EP3 receptor with muskelin 査読

    H Hasegawa, H Katoh, H Fujita, K Mori, M Negishi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   276 ( 1 )   350 - 354   2000年09月( ISSN:0006-291X

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    掲載種別:研究論文(学術雑誌)  

    By using the yeast two-hybrid system, muskelin was found to bind with the carboxy-terminal tail of the prostaglandin EP3 receptor alpha isoform but not with either the beta or gamma isoform. A direct interaction between the carboxy-terminal tail of the alpha isoform and muskelin was confirmed in vitro using recombinant fusion proteins, Analysis by confocal microscopy indicated that the isoform and muskelin were distributed at the plasma membrane in transfected cells. When the isoform was stimulated by agonist, the receptor was internalized in the cells expressing the receptor alone, but this internalization was partially inhibited by the cotransfection with muskelin, Furthermore, muskelin enhanced the Gi activity of the isoform, Thus, muskelin appears to be an isoform-specific anchoring protein for the EP3 receptor. (C) 2000 Academic Press.

    DOI: 10.1006/bbrc.2000.3467

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  • Gα<sub>12</sub> and Gα<sub>13</sub> inhibit Ca<sup>2+</sup>-dependent exocytosis through Rho/Rho- associated kinase-dependent pathway 査読

    Y. Yamaguchi, H. Katoh, H. Yasui, J. Aoki, K. Nakamura, M. Negishi

    Journal of Neurochemistry   75 ( 2 )   708 - 717   2000年08月( ISSN:0022-3042

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1046/j.1471-4159.2000.0750708.x

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  • Immunohistochemical localization of prostaglandin EP3 receptor in the rat nervous system 査読

    K Nakamura, T Kaneko, Y Yamashita, H Hasegawa, H Katoh, M Negishi

    JOURNAL OF COMPARATIVE NEUROLOGY   421 ( 4 )   543 - 569   2000年06月( ISSN:0021-9967

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    掲載種別:研究論文(学術雑誌)  

    The prostaglandin EP3 receptor (EP3R) subtype is believed to mediate large portions of diverse physiologic actions of prostaglandin E-2 in the nervous system. However, the distribution of EP3R protein has not yet been unveiled in the peripheral or central nervous systems. The authors raised a polyclonal antibody against an amino-terminal portion of rat EP3R that recognized specifically the receptor protein. In this study, immunoblotting analysis with this antibody showed several immunoreactive bands with different molecular weights in rat brain extracts and in membrane fractions of recombinant EP3R-expressing culture cells, and treatment with N-glycosidase shifted those immunoreactive bands to an apparently single band with a lower molecular weight, suggesting that EP3R proteins are modified posttranslationally with carbohydrate moieties of various sizes. The authors performed immunohistochemical investigation of EP3R in the rat brain, spinal cord, and peripheral ganglia by using the antibody. EP3R-like immunoreactivity was observed in many and discrete regions of the rostrocaudal axis of the nervous system. The signals were particularly strong in the anterior, intralaminar, and midline thalamic nuclear groups; the median preoptic nucleus; the medial mammillary nucleus; the superior colliculus; the periaqueductal gray; the lateral parabrachial nucleus; the nucleus of the solitary tract; and laminae I and II of the medullary and spinal dorsal horns. Sensory ganglia, such as the trigeminal, dorsal root, and nodose ganglia, contained many immunopositive neurons. Neuronal cells in the locus coeruleus and raphe nuclei exhibited EP3R-like immunoreactivity. This suggests that EP3R plays regulatory roles in the noradrenergic and serotonergic monoamine systems. Autonomic preganglionic nuclei, such as the dorsal motor nucleus of the vagus nerve, the spinal intermediolateral nucleus, and the sacral parasympathetic nucleus, also contained neuronal cell bodies with the immunoreactivity, implying modulatory functions of EP3R in the central autonomic nervous system. The characteristic distribution of EP3R provides valuable information on the mechanisms for various physiologic actions of prostaglandin E-2 in the central and peripheral nervous systems. J. Comp. Neurol. 421:543-569, 2000. (C) 2000 Wiley-Liss, Inc.

    DOI: 10.1002/(SICI)1096-9861(20000612)421:4<543::AID-CNE6>3.0.CO;2-3

    PubMed

  • Different membrane targeting of prostaglandin EP3 receptor isoforms dependent on their carboxy-terminal tail structures 査読

    H Hasegawa, H Katoh, Y Yamaguchi, K Nakamura, S Futakawa, M Negishi

    FEBS LETTERS   473 ( 1 )   76 - 80   2000年05月( ISSN:0014-5793

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    掲載種別:研究論文(学術雑誌)  

    Mouse prostaglandin EP3 receptor consists of three isoforms, EP3 alpha, beta and gamma, with different carboxy-terminal tails. To assess the role of their carboxy-terminal tails in membrane targeting, we examined subcellular localization of myc-tagged EP3 isoforms expressed in MDCK cells. Two isoforms, EP3 alpha and EP3 beta, were localized in the intracellular compartment but not in the plasma membrane, while the EP3 gamma isoform was found in the lateral plasma membrane and in part in the intracellular compartment. Mutant EP3 receptor lacking the carboxy-terminal tail,vas localized in the intracellular compartment but not in the plasma membrane. Thus, EP3 isoforms differ in subcellular targeting, and the carboxy-terminal tails play an important role in determination of the membrane targeting of EP3 receptor. (C) 2000 Federation of European Biochemical Societies.

    DOI: 10.1016/S0014-5793(00)01508-8

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  • Molecular decipherment of Rho effector pathways regulating tight-junction permeability 査読

    H Fujita, H Katoh, H Hasegawa, H Yasui, J Aoki, Y Yamaguchi, M Negishi

    BIOCHEMICAL JOURNAL   346   617 - 622   2000年03月( ISSN:0264-6021

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    掲載種別:研究論文(学術雑誌)  

    We reported recently that the activation of RhoA induced an increase in transepithelial electrical resistance (TER). To clarify effecters of Rho for this RhoA-induced regulation of tight-junction permeability, we introduced two effector-loop mutants of constitutively active RhoA(V14), RhoA(V14/L40) and RhoA(V14/C42), into Mardin-Darby canine kidney cells in an isopropyl beta-D-thiogalactoside-inducible expression system. RhoA(V14) and the two effector-loop mutants interacted in vitro with the Rho-binding domain of Rho-associated kinase, ROK alpha. Next we examined two parameters of Rho functions, stress-fibre formation and TER elevation, induced by RhoA(V14). Stress-fibre formation was induced by RhoA(V14/C42) but not by RhoA(V14/L40) On the other hand, TER elevation was induced by neither RhoA(V14/L40) nor RhoA(V14/C42). RhoA-associated kinase inhibitor, Y-27632, inhibited both stress-fibre formation and TER elevation induced by RhoA(V14). These results demonstrated that RhoA induced regulation of tight-junction permeability is mediated by Rho-associated kinase and at least one other unidentified effector, the coupling to RhoA being disrupted by mutation at position 40 or 42 in the effector loop.

    DOI: 10.1042/0264-6021:3460617

    PubMed

  • Molecular aspects of functions of prostaglandin E receptors in the CNS 査読

    Negishi, M, Katoh, H, Nakamura, K, Aoki, J, Fujita, H

    Recent Research of Developmental Endocrinology, 1, 133-143   2000年

  • Opposite regulation of transepithelial electrical resistance and paracellular permeability by Rho in Madin-Darby canine kidney cells 査読

    H Hasegawa, H Fujita, H Katoh, J Aoki, K Nakamura, A Ichikawa, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   274 ( 30 )   20982 - 20988   1999年07月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Small GTPase Rho has been thought to be important for the formation and the maintenance of tight junction in epithelial cells, but the role of Rho in the regulation of barrier function of tight junction is not web understood. We here examined whether Rho was involved in the barrier function of tight junction in Madin-Darby canine kidney (MDCK) cells. The activation of prostaglandin EP3 beta receptor, coupled to a Rho activation pathway, induced the increase in transepithelial electrical resistance (TER) but the increase in paracellular flux of mannitol in the preformed monolayer of the MDCK cells expressing the EP3 beta receptor. This effect of the EP3 receptor was mimicked by the expression of constitutively active RhoA but not by active Rad in MDCK cells, using an isopropyl-beta-D-thiogalactoside-inducible expression system. On the other hand, the activation of EP3 beta receptor suppressed the elevation of TER and the decrease in paracellular mannitol flux during Ca2+ switch-induced tight junction formation, whereas the expression of active RhoA or Rad did not apparently affect the TER development in the Ca2+ switch. These results demonstrate that the EP3 receptor and active RhoA regulate permeabilities of ionic and nonionic molecules in opposite directions in the preformed monolayer, and the EP3 receptor suppresses the elevation of TER during the tight junction formation.

    DOI: 10.1074/jbc.274.30.20982

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  • Signal transduction pathway regulating prostaglandin EP3 receptor-induced neurite retraction: requirement for two different tyrosine kinases 査読

    J Aoki, H Katoh, H Yasui, Y Yamaguchi, K Nakamura, H Hasegawa, A Ichikawa, M Negishi

    BIOCHEMICAL JOURNAL   340   365 - 369   1999年06月( ISSN:0264-6021

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    掲載種別:研究論文(学術雑誌)  

    We reported previously that activation of the prostaglandin E receptor EP3 subtype triggered neurite retraction through the small GTPase Rho-, and its target, RhoA-binding kinase alpha. (ROKx)-, dependent pathway in EP3 receptor-expressing PC12 cells. Here we examined the involvement of tyrosine kinases in this pathway in nerve growth factor-differentiate PC12 cells. Tyrphostin; A25, a tyrosine kinase inhibitor, blocked neurite retraction and cell rounding induced by activation of the EP3 receptor, however, it failed to block neurite retraction and cell rounding induced by microinjection of constitutively active RhoA, RhoA(v14), indicating that a tyrphostin-sensitive tyrosine kinase was involved in the pathway from the EP3 receptor to Rho activation. On the other hand, genistein, another tyrosine kinase inhibitor, blocked neurite retraction and cell rounding induced by both activation of the EP3 receptor and microinjection of RhoA(v14). However, genistein did not block neuronal morphological changes induced by microinjection of a constitutively active mutant of ROK alpha. These results indicate that two different tyrosine kinases, tyrphostin A25-sensitive and genistein-sensitive kinases, are involved in the EP3 receptor-mediated neurite retraction acting upstream and downstream of Rho, respectively.

    DOI: 10.1042/0264-6021:3400365

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  • The key amino acid residue of prostaglandin EP3 receptor for governing G protein association and activation steps 査読

    S Satoh, CS Chang, H Katoh, H Hasegawa, K Nakamura, J Aoki, H Fujita, A Ichikawa, M Negishi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   255 ( 1 )   164 - 168   1999年02月( ISSN:0006-291X

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    掲載種別:研究論文(学術雑誌)  

    To assess the role of the conserved DPWXY motif of the seventh transmembrane domain in prostanoid receptor-mediated G protein activation, we have mutated the negatively charged Asp-318 in this motif of the Gi-coupled mouse prostaglandin EP3 receptor to uncharged but polar Asn (EP3-D318N) and to the nonpolar Leu (EP3-D318L). The EP3 agonist and antagonist showed similar binding affinities for the mild-type and two mutant receptors. The wild-type and EP3-D318N receptors but not EP3-D318L receptor associated with Gi in guanine nucleotide- and pertussis toxin-sensitive manners. On the other hand, the wild-type receptor but not two mutant receptors had the ability to stimulate GTPase activity and to inhibit the adenylate cyclase. These findings demonstrate that the chemical nature of the amino acid residue at position 318 of the seventh transmembrane domain of the EP3 receptor dissociates the step of Gi association from that of subsequent Gi activation in the process of the EP3 receptor-Gi coupling (C) 1999 Academic Press.

    DOI: 10.1006/bbrc.1998.0161

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  • Immunocytochemical localization of prostaglandin EP3 receptor in the rat hypothalamus 査読

    K Nakamura, T Kaneko, Y Yamashita, H Hasegawa, H Katoh, A Ichikawa, M Negishi

    NEUROSCIENCE LETTERS   260 ( 2 )   117 - 120   1999年01月( ISSN:0304-3940

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    掲載種別:研究論文(学術雑誌)  

    A rabbit antibody against an N-terminal portion of rat prostaglandin EP3 receptor (EP3R) was produced to examine the distribution of EP3R in the rat hypothalamus. The antibody specifically recognized EP3R proteins in rat brain extract, in membrane fractions of rat kidney, and in membrane fractions of EP3R-expressing culture cells. Intense EP3R-like immunoreactivity was observed in the median preoptic nucleus, medial preoptic area, parastrial nucleus, compact part of the dorsomedial hypothalamic nucleus, and dorsal part of the premammillary nucleus. These results suggest that prostaglandin Ep mediates various actions in the hypothalamus, such as fever induction in the preoptic area, through EP3R. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(98)00962-8

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  • Constitutively active Gα<sub>12</sub>, Gα<sub>13</sub>, and Gα(q) induce rho-dependent neurite retraction through different signaling pathways 査読

    H. Katoh, J. Aoki, Y. Yamaguchi, Y. Kitano, A. Ichikawa, M. Negishi

    Journal of Biological Chemistry   273 ( 44 )   28700 - 28707   1998年10月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.273.44.28700

  • Inhibition of dopamine release by prostaglandin EP3 receptor via pertussis toxin-sensitive and -insensitive pathways in PC12 cells 査読

    K Nakamura, H Katoh, A Ichikawa, M Negishi

    JOURNAL OF NEUROCHEMISTRY   71 ( 2 )   646 - 652   1998年08月( ISSN:0022-3042

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    掲載種別:研究論文(学術雑誌)  

    Prostaglandin EP3 receptor is involved in the inhibition of neurotransmitter release from presynaptic nerve terminals in various tissues. We have examined the regulation of neurotransmitter release by the EP3 receptor using a PC12 cell line that stably expresses the EP3B receptor isolated from bovine adrenal medulla. In the cells, M&B28767, an EP3 agonist, inhibited the 50 mM KCl- or 10 nM bradykinin-induced [H-3]dopamine release in a concentration-dependent manner (10 pM to 0.1 mu M). This inhibition was partially reversed by pretreatment with pertussis toxin, whereas under the same condition, the agonist-induced inhibition of forskolin-stimulated cyclic AMP accumulation was suppressed completely. In contrast, M&B28767 did not affect the high K+ - or bradykinin-induced increase in intracellular Ca2+ concentration. Moreover, M&B28767 also inhibited the [H-3]dopamine release induced by the Ca2+ ionophore ionomycin, and this inhibition was also partially reversed by pretreatment with pertussis toxin. These results indicate that the EP3 receptor is coupled to dual pathways, pertussis toxin-sensitive and -insensitive G-protein pathways, to regulate neurotransmitter release without changing Ca2+ influx in neuronal cells.

    DOI: 10.1046/j.1471-4159.1998.71020646.x

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  • p160 RhoA-binding kinase ROKα induces neurite retraction 査読

    H. Katoh, J. Aoki, A. Ichikawa, M. Negishi

    Journal of Biological Chemistry   273 ( 5 )   2489 - 2492   1998年01月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.273.5.2489

    PubMed

  • Functional role of carboxyl-terminal tail of prostaglandin EP3 receptor in Gi coupling 査読

    H Hizaki, H Hasegawa, H Katoh, M Negishi, A Ichikawa

    FEBS LETTERS   414 ( 2 )   323 - 326   1997年09月( ISSN:0014-5793

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    掲載種別:研究論文(学術雑誌)  

    We recently demonstrated that the mouse EP3 beta receptor and its carboxyl-terminal tail-truncated receptor showed agonist-dependent and full constitutive Gi activities, respectively (Hasegawa, H., Negishi, M. and Ichikawa, A, (1996) J. Biol, Chem, 271, 1857-1860), To assess the role of the carboxyl-terminal tail in the EP3 beta receptor Gi coupling, we constructed a series of mutant receptors with progressively truncated carboxyl-termini. The truncated receptors displayed constitutive Gi activities, the degree of constitutive activity basically correlating with the inverse of the length of the carboxyl-terminal tail, but the sequence between Leu340 and Val347 was mainly contributed to the constitutive activity, Thus, the carboxyl-terminal tail plays an important role in the constraint of the EP3 receptor in its inactive conformation. (C) 1997 Federation of European Biochemical Societies.

    DOI: 10.1016/S0014-5793(97)01020-X

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  • Two isoforms of prostaglandin EP3 receptor exhibiting constitutive activity and agonist-dependent activity in Rho-mediated stress fiber formation 査読

    H Hasegawa, M Negishi, H Katoh, A Ichikawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   234 ( 3 )   631 - 636   1997年05月( ISSN:0006-291X

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    掲載種別:研究論文(学術雑誌)  

    We have cloned two isoforms of the mouse prostaglandin E receptor EP3 subtype, EP3 alpha and EP3 beta, with different carboxyl-terminal tails, produced through alternative splicing. To determine the functional differences between the two isoforms, we examined the role of the isoforms in regulation of the actin cytoskeleton using Mardin-Darby canine kidney cells expressing these isoforms. The EP3 alpha isoform constitutively induced stress fiber formation, independent of an agonist, while the EP3 beta isoform agonist-dependently induced stress fiber formation. Pertussis toxin did not prevent stress fiber formation. This signaling pathway is mediated by Rho, because C3 transferase microinjection inhibited stress fiber formation. Therefore, the physiological significance of these isoforms of the EP3 receptor may lie in their different agonist dependency in Rho-mediated stress fiber formation via a pertussis toxin-insensitive G protein. (C) 1997 Academic Press.

    DOI: 10.1006/bbrc.1997.6655

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  • Prostaglandin E receptor EP3 subtype induces neurite retraction via small GTPase Rho 査読

    H Katoh, M Negishi, A Ichikawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   271 ( 47 )   29780 - 29784   1996年11月( ISSN:0021-9258

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    掲載種別:研究論文(学術雑誌)  

    Prostaglandin E receptor EP3 subtype is widely distributed in the nervous system and is specifically localized to neurons, suggesting that the EP3 receptor plays important roles in the nervous system. We established a PC12 cell line that stably expresses the EP3B receptor isoform isolated from bovine adrenal chromaffin cells and examined the effect of agonist stimulation on the neuronal morphology of the PC12 cells, In the differentiated cells, M&B28767, an EP3 agonist, caused neurite retraction in a pertussis toxin-insensitive manner, 12-O-Tetradecanoylphorbol-13-acetate (TPA) also induced neurite retraction. However, when protein kinase C was down-regulated by long term exposure to TPA, TPA failed to induce neurite retraction, while the EP3B receptor-mediated retraction occurred normally, Clostridium botulinum C3 exoenzyme completely inhibited both EP3 agonist- and TPA-induced neurite retraction when microinjected into the cells, indicating that the morphological effect of the EP3B receptor is dependent on Rho activity, Thus, the activation of the EP3B receptor induced neurite retraction through a protein kinase C-independent Rho-activation pathway.

    DOI: 10.1074/jbc.271.47.29780

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  • Characterization of the signal transduction of prostaglandin E receptor EP1 subtype in cDNA-transfected Chinese hamster ovary cells.

    H Katoh, A Watabe, Y Sugimoto, A Ichikawa, M Negishi

    Biochimica et biophysica acta   1244 ( 1 )   41 - 8   1995年05月( ISSN:0006-3002

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    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    We examined the signal transduction of mouse prostaglandin E receptor EP1 subtype using Chinese hamster ovary cells stably expressing the cloned EP1. Sulprostone, an EP1 agonist, induced a rapid increase in intracellular Ca2+ concentration in the EP1-expressing cells. Most of the increase was abolished by removal of extracellular Ca2+, and was insensitive to U-73122, a phospholipase C inhibitor. Sulprostone stimulated phosphatidylinositol hydrolysis, but this stimulation was abolished by removal of extracellular Ca2+, indicating that EP1-stimulated phosphatidylinositol hydrolysis is the result of extracellular Ca2+ influx. Thus, the signal transduction of EP1 is extracellular Ca2+ entry through a pathway independent of phospholipase C activation. We further examined the regulation of the signal transduction of EP1 having potential phosphorylation sites for either protein kinase C or protein kinase A. Short-term exposure of the cells to 12-O-tetradecanoylphorbol 13-acetate (TPA) completely suppressed the sulprostone-induced increase in intracellular Ca2+ concentration, while forskolin or dibutyryl cAMP did not affect it, suggesting that protein kinase C but not protein kinase A is involved in the regulation of the EP1 signal transduction. Furthermore, long-term exposure to TPA decreased PGE2 protein kinase A is involved in the regulation of the EP1 signal transduction. Furthermore, long-term exposure to TPA decreased PGE2 binding activity of EP1 due to the reduction of the EP1 mRNA level. Protein kinase C induces short- and long-term desensitization of EP1.

    PubMed

  • CHARACTERIZATION OF THE SIGNAL-TRANSDUCTION OF PROSTAGLANDIN-E RECEPTOR EP1 SUBTYPE IN CDNA-TRANSFECTED CHINESE-HAMSTER OVARY CELLS 査読

    H KATOH, A WATABE, Y SUGIMOTO, A ICHIKAWA, M NEGISHI

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   1244 ( 1 )   41 - 48   1995年05月( ISSN:0304-4165

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    掲載種別:研究論文(学術雑誌)  

    We examined the signal transduction of mouse prostaglandin E receptor EP1 subtype using Chinese hamster ovary cells stably expressing the cloned EP1. Sulprostone, an EP1 agonist, induced a rapid increase in intracellular Ca2+ concentration in the EP1-expressing cells. Most of the increase was abolished by removal of extracellular Ca2+, and was insensitive to U-73122, a phospholipase C inhibitor. Sulprostone stimulated phosphatidylinositol hydrolysis, but this stimulation was abolished by removal of extracellular Ca2+, indicating that EP1-stimulated phosphatidylinositol hydrolysis is the result of extracellular Ca2+ influx. Thus, the signal transduction of EP1 is extracellular Ca2+ entry through a pathway independent of phospholipase C activation. We further examined the regulation of the signal transduction of EP1 having potential phosphorylation sites for either protein kinase C or protein kinase A. Short-term exposure of the cells to 12-O-tetradecanoylphorbol 13-acetate (TPA) completely suppressed the sulprostone-induced increase in intracellular Ca2+ concentration, while forskolin or dibutyryl cAMP did not affect it, suggesting that protein kinase C but not protein kinase A is involved in the regulation of the EP1 signal transduction. Furthermore, long-term exposure to TPA decreased PGE(2) binding activity of EP1 due to the reduction of the EP1 mRNA level. Protein kinase C induces short- and long-term desensitization of EP1.

    DOI: 10.1016/0304-4165(94)00182-W

    PubMed

    J-GLOBAL

▼全件表示

書籍等出版物

  • 食物繊維と臓器相関

    山口一樹, 加藤裕教, 木村郁夫( 担当: 共著)

    科学評論者「消化器・肝臓内科」11 (4) 436- 444  2022年04月 

  • 腸内細菌叢と肥満症

    北野(大植)隆司, 加藤裕教, 木村郁夫( 担当: 共著)

    実験医学増刊 「個人差の理解へ向かう肥満症研究」  2021年 

  • アミノ酸トランスポーターxCT阻害薬のがん細胞における二面性

    加藤 裕教

    日本薬理学雑誌  2019年02月 

  • 京大初!フロンティア生命科学

    加藤 裕教( 担当: 分担執筆 ,  範囲: 5章 身体を保つ仕組み 代謝とホルモン)

    講談社  2018年03月 

  • 低分子量Gタンパク質RhoGによるシグナル伝達

    加藤裕教

    日本生化学会  2012年07月 

     詳細を見る

    著書種別:学術書  

  • Dockファミリータンパク質による細胞形態・運動の制御

    加藤裕教

    日本生化学会  2009年08月 

     詳細を見る

    著書種別:学術書  

  • アクチン細胞骨格系の制御機構 RhoファミリーGタンパク質

    根岸 学, 加藤裕教

    実験医学 形と運動を司る細胞のダイナミクス(羊土社)  2006年08月 

     詳細を見る

    著書種別:学術書  

  • RhoファミリーのGEFとGAP

    根岸 学, 加藤裕教

    共立出版  2006年06月 

     詳細を見る

    著書種別:学術書  

  • 神経軸索ガイダンス分子、セマフォリンの作用機構

    根岸 学, 加藤裕教

    共立出版  2005年02月 

     詳細を見る

    著書種別:学術書  

  • PP5の新しいシグナル伝達経路

    根岸 学, 加藤裕教

    細胞工学(学研メディカル秀潤社)  2004年05月 

     詳細を見る

    著書種別:学術書  

  • 軸索ガイダンスに関与するアダプター関連分子

    根岸 学, 加藤裕教

    医学書院  2004年04月 

     詳細を見る

    著書種別:学術書  

  • RhoG標的タンパク質ELMOによるRac活性制御

    加藤裕教, 根岸 学

    わかる実験医学シリーズ 細胞骨格・運動がわかる(羊土社)  2004年04月 

     詳細を見る

    著書種別:学術書  

  • 低分子量G蛋白質Rhoファミリー:神経回路形成

    根岸 学, 加藤裕教

    共立出版  2004年03月 

     詳細を見る

    著書種別:学術書  

  • RhoGによる新しいRac1活性化機構

    加藤裕教, 根岸 学

    実験医学(羊土社)  2003年11月 

     詳細を見る

    著書種別:学術書  

▼全件表示

MISC(その他記事)

  • SGEFによる細胞運動の制御とScribbleの抑制作用

    山本佳央理, 根岸 学, 加藤裕教

    第40回日本分子生物学会 第90回日本生化学会 合同年会   2017年12月

  • 脳由来神経栄養因子(BDNF)によるR-Rasの活性化と軸索形態制御の分子機構

    梅田健太郎, 加藤裕教, 根岸 学

    第40回日本分子生物学会 第90回日本生化学会 合同年会   2017年12月

  • Molecular mechanisms underlying the regulateon of R-Ras activation and R-Ras-mediated axon branching formation in primary cultured cortical neurons.

    梅田健太郎, 加藤裕教, 根岸 学

    Society for Neuroscience 2017   2017年11月

  • 神経細胞の軸索の形態制御における、R-Rasの上流シグナルの解明

    梅田健太郎, 加藤裕教, 根岸 学

    第64回日本生化学会近畿支部例会   2017年05月

  • BDNF promotes the formation of axonal morphology through Ras-GRF1-mediated R-Ras activation.

    梅田健太郎, 加藤裕教, 根岸 学

    British Neuroscience Association 2017   2017年04月

  • EphA2によるグリオブラストーマ細胞増殖制御に関わる分子の探索 査読

    濱岡裕穂, 根岸 学, 加藤裕教

    第89回 日本生化学会   2016年09月

  • グルコース欠乏によるグリオブラストーマの細胞死誘導機構の解明 査読

    郷司剛央, 根岸 学, 加藤裕教

    第89回 日本生化学会   2016年09月

  • RSKによるEphA2のリン酸化とグリオブラストーマ細胞の増殖制御

    濱岡裕穂, 根岸 学, 加藤裕教

    第63回 日本生化学会 近畿支部会   2016年05月

  • EphA2のリガンド非依存的シグナルによるグリオブラストーマ細胞の増殖制御

    濱岡裕穂, 根岸 学, 加藤裕教

    第38回日本分子生物学会 第88回日本生化学会 合同大会   2015年12月

  • The role of EphA2 in regulating HGF-induced epithelial morphogenesis in three-dimensional culture.

    K. Harada, M. Negishi, H. Katoh

    MOLECULAR BIOLOGY OF THE CELL   25   2014年12月( ISSN:1059-1524 ( eISSN:1939-4586

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • HGF刺激による上皮細胞の三次元形態形成におけるEphA2の役割

    原田耕平, 根岸 学, 加藤裕教

    第87回日本生化学会大会   2014年10月

  • RhoG特異的活性化因子SGEFのチロシンリン酸化による機能制御

    奥山裕介, 原田耕平, 根岸 学, 加藤裕教

    第87回日本生化学会大会   2014年10月

  • Dock4とSH3YL1との結合によるがん細胞の運動制御

    小林大師, 原田耕平, 根岸 学, 加藤裕教

    第86回日本生化学会大会   2013年09月

  • RacGEF Dock4の機能制御と病態との関連

    加藤裕教, 根岸 学

    第86回日本生化学会大会   2013年09月

  • がん細胞におけるEphA2とEphB6の相互作用の解析

    赤田麻衣, 原田耕平, 根岸 学, 加藤裕教

    第86回日本生化学会大会   2013年09月

  • EphA2受容体に結合するEphexin4の機能 査読

    加藤裕教, 根岸 学

    第85回日本生化学会大会   2012年12月

  • EphA2の897番目のセリンのリン酸化は、Ephexin4/RhoGによるがん細胞の運動とアノイキス耐性を制御する

    川合宏武, 小林大師, 平本-山木奈央, 原田耕平, 根岸 学, 加藤裕教

    第85回日本生化学会大会   2012年12月

  • Ephexin4-RhoGシグナル制御におけるScribbleの役割

    原田耕平, 根岸 学, 加藤裕教

    第85回日本生化学会大会   2012年12月

  • 大脳皮質神経前駆細胞の増殖を制御する分子機構の解明

    加藤 裕教

    第一三共生命科学研究振興財団研究報告集   28   69 - 76   2012年

     詳細を見る

  • The Rac-specific GEF Dock4 controls dendritic spine formation in hippocampal neurons 査読

    S. Ueda, M. Negishi, H. Katoh

    the 41th annual meeting of the Society for Neuroscience 2011   2011年11月

  • EphA2受容体による細胞運動の制御 査読

    加藤裕教, 根岸 学

    第84回日本生化学会大会   2011年09月

  • 海馬ニューロンの樹状突起スパイン形成におけるRac活性化因子Dock4の役割 査読

    上田修平, 根岸 学, 加藤裕教

    第84回日本生化学会大会   2011年09月

  • Rac1活性化因子Dock4は海馬ニューロンの樹状突起スパイン形成を制御する 査読

    上田修平, 根岸 学, 加藤裕教

    第34回日本神経科学大会   2011年09月

  • The F-BAR protein rapostlin regulates dendritic spine formation in hippocampal neurons 査読

    Yohei Wakita, Tetsuhiro Kakimoto, Hironori Katoh, Manabu Negishi

    Journal of Biological Chemistry   286 ( 37 )   32672 - 32683   2011年09月( ISSN:0021-9258

     詳細を見る

    Pombe Cdc15 homology proteins, characterized by Fer/CIP4 homology Bin-Amphiphysin-Rvs/extended Fer/CIP4 homology (F-BAR/EFC) domains with membrane invaginating property, play critical roles in a variety of membrane reorganization processes. Among them, Rapostlin/formin-binding protein 17 (FBP17) has attracted increasing attention as a critical coordinator of endocytosis. Here we found that Rapostlin was expressed in the developing rat brain, including the hippocampus, in late developmental stages when accelerated dendritic spine formation and maturation occur. In primary cultured rat hippocampal neurons, knockdown of Rapostlin by shRNA or overexpression of Rapostlin-QQ, an F-BAR domain mutant of Rapostlin that has no ability to induce membrane invagination, led to a significant decrease in spine density. Expression of shRNA-resistant wild-type Rapostlin effectively restored spine density in Rapostlin knockdown neurons, whereas expression of Rapostlin deletion mutants lacking the protein kinase C-related kinase homology region 1 (HR1) or Src homology 3 (SH3) domain did not. In addition, knockdown of Rapostlin or overexpression of Rapostlin-QQ reduced the uptake of transferrin in hippocampal neurons. Knockdown of Rnd2, which binds to the HR1 domain of Rapostlin, also reduced spine density and the transferrin uptake. These results suggest that Rapostlin and Rnd2 cooperatively regulate spine density. Indeed, Rnd2 enhanced the Rapostlin-induced tubular membrane invagination. We conclude that the F-BAR protein Rapostlin, whose activity is regulated by Rnd2, plays a key role in spine formation through the regulation of membrane dynamics. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

    DOI: 10.1074/jbc.M111.236265

    PubMed

  • The F-BAR ドメイン蛋白質Rapostlinは海馬ニューロンにおいてエンドサイトーシスと樹状突起スパイン形成を制御する 査読

    脇田洋平, 柿本哲宏, 加藤裕教, 根岸 学

    第34回日本神経科学大会   2011年09月

  • The F-BAR protein Rapostlin regulates endocytosis and dendritic spine formation in hippocampal neurons

    Yohei Wakita, Tetsuhiro Kakimoto, Hironori Katoh, Manabu Negishi

    NEUROSCIENCE RESEARCH   71   E135 - E135   2011年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.1016/j.neures.2011.07.582

  • The Rac activator Dock4 regulates dendritic spine formation in hippocampal neurons

    Shuhei Ueda, Manabu Negishi, Hironori Katoh

    NEUROSCIENCE RESEARCH   71   E336 - E336   2011年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.1016/j.neures.2011.07.1471

  • Ephexin4はがん細胞におけるアノイキス制御に関与する 査読

    原田耕平, 山木奈央, 根岸 学, 加藤裕教

    第83回日本生化学会大会、第33回日本分子生物学会大会 合同大会   2010年12月

  • The F-BAR domain is important for the regulation of endocytosis and spine formation by Rapostlin in hippicampal neurons 査読

    脇田洋平, 柿本哲宏, 加藤裕教, 根岸 学

    第83回日本生化学会大会、第33回日本分子生物学会大会 合同大会   2010年12月

  • β2-chimaerinはEph受容体と結合して細胞運動を抑制する 査読

    竹内真吾, 山木菜央, 岩里琢治, 根岸 学, 加藤裕教

    第82回日本生化学会大会   2009年10月

  • 樹状突起の形態形成におけるDockファミリーの役割

    加藤裕教, 上田修平, 倉本和也, 藤本聡志, 根岸 学

    第32回日本神経科学大会   2009年09月

  • 細胞運動におけるEph受容体によるRac活性制御

    加藤裕教

    第61回日本細胞生物学会大会   2009年06月

  • Dockファミリーによる細胞形態・運動の制御

    加藤裕教

    生化学   81 ( 8 )   711 - 716   2009年( ISSN:0037-1017

     詳細を見る

  • The role of Dock family Rho-GEFs in dendrite morphogenesis

    Hironori Katoh, Shuhei Ueda, Kazuya Kuramoto, Satoshi Fujimoto, Manabu Negishi

    NEUROSCIENCE RESEARCH   65   S13 - S13   2009年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.1016/j.neures.2009.09.1547

  • RhoG regulates neural progenitor cell proliferation through PI3K 査読

    S. FUJIMOTO, M. NEGISHI, H. KATOH

    the 38th annual meeting of the Society for Neuroscience   2008年11月

  • The Cdc42 activator Zizimin1/Dock9 regulates dendritic development in hippocampal neurons 査読

    K. KURAMOTO, M. NEGISHI, H. KATOH

    the 38th annual meeting of the Society for Neuroscience   2008年11月

  • Lysophosphatidic acid and thrombin receptors require both Gα12 and Gα13 to regulate axonal morphology in hippocampal neurons 査読

    J. YAMAZAKI, H. KATOH, M. NEGISHI

    the 38th annual meeting of the Society for Neuroscience   31 ( 12 )   2216 - 2222   2008年( ISSN:0918-6158

     詳細を見る

  • An F-BAR/EFC protein Rapostlin regulates dendritic spine morphogenesis 査読

    T. KAKIMOTO, H. KATOH, M. NEGISHI

    the 37th annual meeting of the Society for Neuroscience   2007年11月

  • The role of Dock4, a Rac activator, in neuronal development 査読

    K. HIRAMOTO, S. UEDA, M. NEGISHI, H. KATOH

    the 37th annual meeting of the Society for Neuroscience   2007年11月

  • An F-BAR/EFC protein rapostlin regulates dendritic spine development

    Tetsuhiro Kakimoto, Hironori Katoh, Manabu Negishi

    NEUROSCIENCE RESEARCH   58   S131 - S131   2007年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • How does ephrinB3/EphA4 signaling regulate motor-circuit formation'?

    Takuji Iwasato, Hironori Katoh, Hiroshi Nishimaru, Yukio Ishikawa, Haruhisa Inoue, Y. M. Saito, R. Ando, M. Iwama, Ryosuke Takahashi, Manabu Negishi, Shigeyoshi Itohara

    NEUROSCIENCE RESEARCH   58   S204 - S204   2007年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • Sema4D/Plexin-B1 activates PTEN via R-Ras GAP activity, inducing growth cone collapse

    Yuri Ito, Izumi Oinuma, Hironori Katoh, Manabu Negishi

    NEUROSCIENCE RESEARCH   58   S146 - S146   2007年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • RhoG regulates neural progenitor cell proliferation in mouse cerebral cortex

    Satoshi Fujimoto, Manabu Negishi, Hironori Katoh

    NEUROSCIENCE RESEARCH   58   S200 - S200   2007年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • RhoファミリーのGEFとGAP (細胞骨格と接着) -- (Rhoファミリー)

    根岸学, 加藤裕教

    蛋白質核酸酵素   51 ( 6 )   693 - 698   2006年05月( ISSN:0039-9450

     詳細を見る

  • Pragmin, a novel effector of Rnd2 GTPase, stimulates RhoA activity 査読

    H Tanaka, H Katoh, M Negishi

    JOURNAL OF BIOLOGICAL CHEMISTRY   281 ( 15 )   10355 - 10364   2006年04月( ISSN:0021-9258

     詳細を見る

    The Rho family of small GTPases has been implicated in the reorganization of actin cytoskeleton and subsequent morphological changes in various cells. Rnd2 is a member of the Rnd subfamily, comprising Rnd1, Rnd2, and Rnd3. In contrast to Rnd1 and Rnd3, displaying an antagonistic action for RhoA signaling, signaling pathways of Rnd2 are not well known. Here we have performed a yeast two-hybrid screen using Rnd2 as bait and identified a novel Rnd2 effector protein, predominantly expressed in neurons, including cortical and hippocampal neurons. We named it Pragmin (pragma of Rnd2). In in vivo and in vitro binding assays, Pragmin specifically binds to Rnd2 among the Rho family GTPases in a GTP-dependent manner. Rnd2-bound Pragmin significantly stimulates RhoA activity and induces cell contraction through RhoA and the Rho-kinase pathway in HeLa cells. In PC12 cells, expressing Pragmin inhibits nerve growth factor-induced neurite outgrowth in response to Rnd2, and knock-down of Pragmin by Pragmin-specific small interfering RNA enhances neurite elongation. Therefore, Rnd2 regulates neurite outgrowth by functioning as the RhoA activator through Pragmin, in contrast to Rnd1 and Rnd3 inhibiting RhoA signaling.

    DOI: 10.1074/jbc.M511314200

  • High frequency of ophthalmic malformation and altered thermal pain response in mice lacking apelin

    M Kakuda, A Kasai, N Shintani, H Hashimoto, H Katoh, T Matsuda, A Baba

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   238P - 238P   2006年( ISSN:1347-8613

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • Semaphorin 4D inhibits beta 1 integrin activity through the R-RasGAP activity of Plexin-B1

    Izumi Oinuma, Hironori Katoh, Manabu Negishi

    NEUROSCIENCE RESEARCH   55   S185 - S185   2006年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • Sema4D/Plexin-B1 activates GSK-3 beta via R-Ras GAP activity, inducing growth cone collapse

    Yuri Ito, Izumi Oinuma, Hironori Katoh, Manabu Negishi

    NEUROSCIENCE RESEARCH   55   S82 - S82   2006年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • Pragmin, a novel effector of Rnd2 GTPase, stimulates RhoA activity and regulates neurite outgrowth

    Hironori Katoh, Hiroko Tanaka, Manabu Negishi

    NEUROSCIENCE RESEARCH   55   S183 - S183   2006年( ISSN:0168-0102

     詳細を見る

    掲載種別:研究発表ペーパー・要旨(国際会議)  

  • Differential distribution of RhoG effector Elmo1 and Elmo2 in the developing mouse brain 査読

    Hironori Katoh, Chisaki Ishida, Satoshi Fujimoto, Yukio Ishikawa, Manabu Negishi

    the 35th annual meeting of the Society for Neuroscience   2005年11月

  • 神経軸索ガイダンス分子,セマフォリンの作用機構

    根岸学, 加藤裕教

    蛋白質核酸酵素   50 ( 2 )   141 - 147   2005年02月( ISSN:0039-9450

     詳細を見る

  • The semaphorin 4D receptor Plexin-B1 functions as a GTPase activating protein for R-Ras 査読

    Hironori Katoh, Izumi Oinuma, Yukio Ishikawa, Manabu Negishi

    the 34th annual meeting of the Society for Neuroscience   2004年10月

     詳細を見る

  • PP5の新しいシグナル伝達経路 (特集 解明が進むプロテインホスファターゼ--その新機能から疾患への関わりまで) -- (セリン/スレオニンホスファターゼ)

    根岸学, 加藤裕教

    細胞工学   23 ( 5 )   538 - 540   2004年05月( ISSN:0287-3796

     詳細を見る

  • 軸索ガイダンスに関与するアダプター関連分子 (特集・アダプタータンパク)

    根岸学, 加藤裕教

    生体の科学   55 ( 2 )   111 - 117   2004年03月( ISSN:0370-9531

  • 低分子量G蛋白質Rhoファミリー 神経回路形成 (神経回路の機能発現のメカニズム) -- (神経回路形成の分子的基盤)

    根岸学, 加藤裕教

    蛋白質核酸酵素   49 ( 3 )   331 - 336   2004年02月( ISSN:0039-9450

     詳細を見る

  • Involvement of RND1 GTPase in dendritic spine formation in rat hippocampal neurons Expression and function of a small GTP - binding protein, rnd2 in radially migrating cells in the developing cerebral cortex 査読

    Y.Ishikawa, H.Katoh, M.Negishi

    the 33th annual meeting of the Society for Neuroscience   2003年11月

  • The small GTPase RhoG regulates neurite outgrowth through Elmo and Dock180-mediated activation of Rac1 査読

    Hironori Katoh, Manabu Negishi

    the 33th annual meeting of the Society for Neuroscience   2003年11月

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