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Signal Transduction and Biological Significance of the Small GTPase Rho

Research Project

Project/Area Number 13002007
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

NARUMIYA Shuh  Kyoto University Faculty of Medicine, Department of Pharmacology, Professor, 医学研究科, 教授 (70144350)

Project Period (FY) 2001 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥652,600,000 (Direct Cost: ¥502,000,000、Indirect Cost: ¥150,600,000)
Fiscal Year 2005: ¥119,600,000 (Direct Cost: ¥92,000,000、Indirect Cost: ¥27,600,000)
Fiscal Year 2004: ¥119,600,000 (Direct Cost: ¥92,000,000、Indirect Cost: ¥27,600,000)
Fiscal Year 2003: ¥127,400,000 (Direct Cost: ¥98,000,000、Indirect Cost: ¥29,400,000)
Fiscal Year 2002: ¥127,400,000 (Direct Cost: ¥98,000,000、Indirect Cost: ¥29,400,000)
Fiscal Year 2001: ¥158,600,000 (Direct Cost: ¥122,000,000、Indirect Cost: ¥36,600,000)
KeywordsRho / Actin / microtubules / Cell motility / Cell cycle / Cdc42 / mDia / ROCK / ミオシン / 細胞分裂 / KOマウス / ROCK(Rho kinase) / 神経突起形成 / ROCK-II欠損マウス / 染色体分離 / Rac / 神経突起 / 細胞接着 / アクチン細胞骨格 / citron-kinase / 細胞移動 / 細胞質分裂
Research Abstract

1.The property and function of mDial were studied. It was shown: (1) mDial produces long straight actin filament in the cell by exerting its actin nucleation and polymerization activity, (2) mDial links Rho to Rac ac)tivation through c-Src-Cas-DOCK180 pathway, and antagonizes contractile action of the Rho-ROCK pathway, (3) the balance of the mDial and ROCK determines the cell morphology, a typical example being neurite extension in which the Rho-mDial pathwa extends and the Rho-ROCK pathway retracts neurites dependent on the level of GTP-Rho, and (4) mDial regulates polarity and adhesion turnover in migrating cells and functions in directed cell migration.
2.The regulation and function of Rho GTPases in cell division were studied. It was shown: (1) Cdc42 is specifically activated in metaphase and this activation is regulated by a Rho-GEF, ECT2, and a Rho-GAP, MgcRacGAP, (2) Cdc42 acts on a mDia isoform, mDia3, present at the kinetochore, and this pathway contribute biorient binding of the spndle microtubules to the knetochore, thereby regulating chromosome congression in metaphase.
3.Mice deficient in either one of the two ROCK isoforms, ROCK-I or ROCK-II, individually, were generated and their phenotypes were studied. This study has elucidated the importance of ROCK-II in homeostatic regulation of placental circulation and that of both isoforms in tissue closure during development. The absence of ROCK-II induces throm
4.
5.bosis in the placenta and causes intrauterine growth retardation, and the loss of either isoform results in open eye at birth and omphalocele due to impaied closure of the eyelids and ventral body wall.

Report

(6 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (42 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (24 results) Publications (18 results)

  • [Journal Article] Rho GTPases in animal cell mitosis.2006

    • Author(s)
      Narumiya S, Yasuda, S
    • Journal Title

      Curr.Opin.Cell Biol. 18・2

      Pages: 199-205

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.2005

    • Author(s)
      Oceguera-Yanez, F. et al.
    • Journal Title

      J. Cell Biol. 168

      Pages: 221-232

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.2005

    • Author(s)
      Shimizu, Y. et al.
    • Journal Title

      J. Cell Biol. 168

      Pages: 941-953

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.2005

    • Author(s)
      Oceguera-Yanez, F., Kimura, K., Yasuda, S., Higashida, C., Kitamura, T., Hiraoka, Y., Haraguchi, T., Narumiya, S.
    • Journal Title

      J. Cell Biol. 168

      Pages: 221-232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.2005

    • Author(s)
      Shimizu, Y., Thumkeo, D., Keel, J., Ishizaki, T., Oshima, H., Oshima, M., Noda, Y., Matsumura, F., Taketo, M.M., Narumiya, S.
    • Journal Title

      J. Cell Biol. 168

      Pages: 941-953

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ROCK-I and ROCK-II cooperatively regulate closure of eyelid and ventral body wall in mouse embryo.2005

    • Author(s)
      Thumkeo, D. et al.
    • Journal Title

      Genes Cells, 10・8

      Pages: 825-834

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Local change in phospholipid composition at the cleavage furrow is essential for completion of cytokinesis.2005

    • Author(s)
      Emoto, K. et al.
    • Journal Title

      J.Biol.Chem. 280・45

      Pages: 37901-37907

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Possible role of Rho/Rhotekin signaling in mammalian septin organization.2005

    • Author(s)
      Ito, H.et al.
    • Journal Title

      Oncogene 24

      Pages: 7064-7072

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Suppression of allergic inflammation by prostaglandin E receptor subtype EP3.2005

    • Author(s)
      Kunikata T, et al.
    • Journal Title

      Nature Immunology 6・5

      Pages: 524-531

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Thromboxane A_2 and prostaglandin F_<2a> mediate inflammatory tachycardia.2005

    • Author(s)
      Takayama, K. et al.
    • Journal Title

      Nature Medicine 11・5

      Pages: 562-566

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.2005

    • Author(s)
      Oceguera-Yanez, F., et al.
    • Journal Title

      J.Cell Biol. 168

      Pages: 221-232

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.2005

    • Author(s)
      Shimizu, Y., et al.
    • Journal Title

      J.Cell Biol 168

      Pages: 941-953

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Actin polymerization-driven molecular movement of mDia1 in living cells.2004

    • Author(s)
      Higashida, C. et al.
    • Journal Title

      Science 303

      Pages: 2007-2010

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cdc42 and mDia3 regulate microtubule attachment to kinetochores.2004

    • Author(s)
      Yasuda, S. et al.
    • Journal Title

      Nature 428

      Pages: 767-771

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Actin polymerization-driven molecular movement of mDial in living cells.2004

    • Author(s)
      Higashida, C., Miyoshi, T., Fujita, A., Oceguera-Yanez, F., Monypenny, J., Ando, Y., Narumiya, S., Watanabe, N.
    • Journal Title

      Science 303

      Pages: 2007-2010

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cdc42 and mDia3 regulate microtubule attachment to kinetochores.2004

    • Author(s)
      Yasuda, S., Oceguera-Yanez, F., Kato, T., Okamoto, M., Yonemura, S., Terada, Y., Ishizaki, T., Narumiya, S.
    • Journal Title

      Nature 428

      Pages: 767-771

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Actin polymerization-driven molecular movement of mDia1 in-living cells.2004

    • Author(s)
      Higashida, C., et al.
    • Journal Title

      Science 303

      Pages: 2007-2010

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cdc42 and mDia3 regulate microtubule attachment to kinetochores.2004

    • Author(s)
      Yasuda, S., et al.
    • Journal Title

      Nature 428

      Pages: 767-771

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A New Look at Rho GTPases in Cell Cycle : Role in Kinetochore-Microtubule Attachment.2004

    • Author(s)
      Narumiya, S., et al.
    • Journal Title

      Cell Cycle 3

      Pages: 855-857

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gα(q/11) signaling induces apoptosis through two pathways involving reduction of Akt phosphorylation and activation of RhoA in HeLa cells.2004

    • Author(s)
      Ueda, H., et al.
    • Journal Title

      Exp Cell Res. 298

      Pages: 207-217

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Control of axon elongation via an SDF-1α/Rho/mDia pathway in cultured cerebellar granule neurons.2003

    • Author(s)
      Arakawa, Y. et al.
    • Journal Title

      J. Cell Biol. 161

      Pages: 381-391

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of axon elongation via an SDF-1a/Rho/mDia pathway in cultured cerebellar granule neurons.2003

    • Author(s)
      Arakawa, Y., Bito, H., Furuyashiki, T., Tsuji, T., Takemoto-Kimura, S., Kimura, K., Nozaki, K., Hashimoto, N., Narumiya, S.
    • Journal Title

      J. Cell Biol. 161

      Pages: 381-391

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts.2002

    • Author(s)
      Tsuji, T. et al.
    • Journal Title

      J. Cell Biol. 157

      Pages: 819-830

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ROCK and mDial antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts.2002

    • Author(s)
      Tsuji, T., Ishizaki, T., Okamoto, M., Higashida, C., Kimura, K., Furuyashiki, T., Arakawa, Y., Birge, R.B., Nakamoto, T., Hirai, H., Narumiya, S.
    • Journal Title

      J. Cell Biol. 157

      Pages: 819-830

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Arakawa, Y., et al.: "Control of axon elongation via an SDF-1α/Rho/mDia pathway in cultured cerebellar granule neurons."Journal of Cell Biology. 161. 381-391 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Dean, T., et al.: "Targeted disrupton of the mouse Rho-associated kinase 2 (mROCK-II) gene results in intrauterine growth retardation and fetal death."Molecular and Cellular Biology. 23. 5043-5055 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashiro, S., et al.: "Citron Kinase, a Rho-dependent Kinase, Induces Di-phosphorylation of Regulatory Light Chain of Myosin II."Mol.Biol.Cell. 14. 1745-1756 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada, A., et al.: "The Core FH2 Domain of Diaphanous related Formins is an elongated barbed-end binding Protein that inhibits Polymerization."Molecular Cell. 13. 511-522 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higashida, C., et al.: "Actin polymerization-driven molecular movement of mDia1 in living cells."Science. In press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasuda, S., et al.: "Cdc42 and mDia3 regulate microtubule attachment to kinetochores."Nature. In press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuji, T. et al.: "ROCK and mDial antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts"Journal of Cell Biology. 157. 819-830 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chevrier, V.et al.: "The Rho-associated protein kinase p160ROCK is required for centrosome positioning"Journal of Cell Biology. 157. 807-817 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furuyashiki, T. et al.: "Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltagegated Ca^<2+> channels"Proceedings of National Academy of Sciecne U.S.A.. 99. 14458-14463 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arakawa, Y. et al.: "Control of axon elongation via an SDF-1α/Rho/mDia pathway in cultured cerebellar granule neurons"Journal of Cell Biology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kabashima, K., et al.: "Prostaglandin E_2-EP4 signaling facilitates initiation of skin immune response by regulating Langerhans cell migration and maturation"Nature Medicine. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Minoshima, Y. et al.: "Phosphorylation of MgcRacGAP by aurora B kinase leads to induction of latent GAP activity towards RhoA during mitosis ; identification of a RhoGAP indispensable for the completion of cytokinesis"Development Cell. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishizaki, T. et al.: "Coordination of microtubules and actin cytoskeleton by a Rho effector, mDia1"Nature Cell Biology. 3. 8-14 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato, T. et al.: "Localization of a mammalian homolog of Diaphanous, mDia1, to the mitotic spindle in HeLa cells"Journal of Cell Science. 114. 775-784 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Carr, D, W. et al.: "Identification of sperm-specific proteins that interact with A-kinase anchoring proteins(AKAPs) in a manner similar to the type II regulatory subunit of PKA"Journal of Biological Chemistry. 276. 17332-17338 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Eda, M.et al.: "Rho-dependent transfer of Citron-kinase to the cleavage furrow of dividing cells"Journal of Cell Science. 114. 3273-3284 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Riveline, D. et al.: "Focal contacts as mechanosensors : Externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism"Journal of Cell Biology. 153. 1175-1186 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ueda, H. et al.: "Gα11 induces caspase-mediated proteolytic activation of Rho-associated kinase, ROCK-I, in HeLa cells"Journal of Biological Chemistry. 276. 42527-42553 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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