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2006 Fiscal Year Final Research Report Summary

Roles of small GTPases in neuronal network formation

Research Project

Project/Area Number 16390021
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto University

Principal Investigator

NEGISHI Manabu  Kyoto Univ., Grad.Sch.Biostudies, Professor, 生命科学研究科, 教授 (60201696)

Co-Investigator(Kenkyū-buntansha) KATOH Hironori  Kyoto Univ., Grad.Sch.Biostudies, Associate Professor, 生命科学研究科, 助教授 (50303847)
Project Period (FY) 2004 – 2006
Keywordssemaphorin / plexin / Rnd / Rho / axon / neurite / R-Ras / GAP
Research Abstract

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 netrins. Plexins function as receptors for repylsive axonal guidance molecules, semaphorins. We have revealed that the semaphorin 4D, Sema4D, receptor Plexin-B1 directly stimulates the intrinsic GAPase activity of R-Ras, which has been shown to promote neurite outgrowth by activating integrins, in response to sema4D. The down regulation of R-Ras activity by the Plexin-B1 is essential for the Sema4D-induced frowth cone collapse in hippocampal neurons. In addition, the downregulation of R-Ras activity is also required for the Sema3A-induced growth cone collapse. Thus, Plexins mediate semaphorin-induced repulsive signaling by acting as a GAP for R-Ras. We have further characterized the downstream signaling of Plexin-B1-mediated R-Ras GAP activity. Sema4D suppressed R-Ras activity in hippocampal neurons and dephosphorylated Akt and … More GSK3 and phosphorylated CRMP-2, a microtubule polumerization stimulator, through its inhibition of R-Ras activity. We also found that Sema3A dephosphorylates Akt and GSK3. Therefore, Plexins inactivate PI-3K and Akt, and activate GSK3 through R-Ras GAP activity, inducing growth cone collapse.
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. 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. Pragmin stimulates RhoA activity in response to Rnd2, inducing cell contraction and neurite retraction. Therefore, Rnd2 regulates neurite outgrowth by functioning as the RhoA activator through Pragmin, in contrast to Rnd1 and Rnd3 inhibiting RhoA signaling. Less

  • Research Products

    (12 results)

All 2007 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] R-Ras controls axon specvification upstream of glycogen synthase kinase-3β through integrin-liked kinase.2007

    • Author(s)
      Izumi Oinuma
    • Journal Title

      The Journal of Biological Chemistry 282・1

      Pages: 303-318

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] R-Ras controls axon specification upstream of glycogen synthase kinase-3β through integrin-linked kinase.2007

    • Author(s)
      Izumi Oinuma
    • Journal Title

      The Journal of Biological Chemistry 282-1

      Pages: 303-318

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activitiy inhibits cell migration by regulating β integrin activity.2006

    • Author(s)
      Izumi Oinuma
    • Journal Title

      The Journal of Cell Biology 173・4

      Pages: 601-613

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sema4D/plexin-B1 activates GSK-3β through R-Ras GAP activity, inducing growth cone collapse.2006

    • Author(s)
      Yuri Ito
    • Journal Title

      EMBO reports 7・7

      Pages: 704-709

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of neuronal morphology by Toca-1, and F-BAR/EFC protein that induces plasma membrane invagination.2006

    • Author(s)
      Tetsuhiro Kakimoto
    • Journal Title

      The Journal of Biological Chemistry 281・39

      Pages: 29042-29053

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activity inhibits cell migration by regulating β integrin activity.2006

    • Author(s)
      Izumi Oinuma
    • Journal Title

      The Journal of Cell Biology 173-4

      Pages: 601-613

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sema4D/plexin-B1 activates GSK-3β through R-Ras GAP activity, inducing growth cone collapse.2006

    • Author(s)
      Yuri Ito
    • Journal Title

      EMBO reports 7-7

      Pages: 704-709

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of neuronal morphology by Toca-1, and F-BAR/EFC protein that induces plasma membrane invagination.2006

    • Author(s)
      Tetsuhiro Kakimoto
    • Journal Title

      The Journal of Biological Chemistry 281-39

      Pages: 29042-29053

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of Racl by RhoG regulates cell migration.2005

    • Author(s)
      Hironori Katoh
    • Journal Title

      Journal of Cell Science 119

      Pages: 56-65

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of Rac1 by RhoG regulates cell migration.2005

    • Author(s)
      Hironori Katoh
    • Journal Title

      Journal of Cell Science 119

      Pages: 56-65

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The Semaphoring 4D receptor Prexin-B1 is a GTPase activating protein for R-Ras.2004

    • Author(s)
      Izumi Oinuma
    • Journal Title

      Science 305

      Pages: 862-865

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras.2004

    • Author(s)
      Izumi Oinuma
    • Journal Title

      Science 305

      Pages: 862-865

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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