Signal Transduction and Biological Significance of the Small GTPase Rho

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 13002007
• Research Category: Grant-in-Aid for Specially Promoted Research
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto 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
• Keywords: Rho / Actin / microtubules / Cell motility / Cell cycle

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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