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Studies on Rho-and Ca^<2+>-dependent signaling mechanisms regulating neuronal actin cytoskeleton

Research Project

Project/Area Number 15300125
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

BITO Haruhiko  The University of Tokyo, Graduate School of Medicine, Associate, 大学院・医学系研究科, 助教授 (00291964)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 2004: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2003: ¥10,300,000 (Direct Cost: ¥10,300,000)
Keywordscalcium / actin / Rho / kinase / cerebellar granule neurons / hippocampal pyramidal neuron / calcium / リン酸化 / CaMK / actin / ROCK / mDia / 軸索
Research Abstract

1.We examined the signaling pathway downstream of Rho that may be involved in regulating axonogenesis in cerebellar granule neurons in primary culture. These were chosen because these neurons have the interesting property of generating two bipolar axons immediately after plating, prior to further development of neurites, thereby greatly facilitating signaling analyses. We elucidated the essential positive role of the SDF-1α/Rho/mDial pathway in controlling the rate of axon elongation. As we previously discovered a negative regulatory role for the Rho/ROCK cascade, our data suggest that appropriate rate of axonogenesis might be tightly controlled by an antagonism between two distinct Rho effectors, ROCK and mDia1.
2.We previously described how synaptic activity-induced calcium mobilization in hippocampal pyramidal neurons triggered actin recruitment to the spines. However, the critical molecules linking calcium with local actin reorganization remained unclear. We here examine whether a novel CaMK we identified as CLICK-III/CaMKIγ was potentially able to fill this role. When overexpressed in vitro, CLICK-III/CaMKIγ was found to be sufficient in promoting and facilitating depolarization-induced neuritogenesis in PC-12 cells.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2004 2003 Other

All Journal Article (11 results) Publications (5 results)

  • [Journal Article] ROCKインヒビター:神経再生ならびに神経変性防止におけるあらたな創薬標的2004

    • Author(s)
      尾藤晴彦
    • Journal Title

      医学のあゆみ 208

      Pages: 469-473

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] ROCK inhibitors as new pharmaceutical targets for neurogenesis and prevention from neurodegeneration2004

    • Author(s)
      Bito H.
    • Journal Title

      Progress in Medicine (in Japanese) 208

      Pages: 469-473

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular cloning and characterization of CLICK-III/CaMKIγ, a novel membrane-anchored neuronal CaMK2003

    • Author(s)
      Takemoto-Kimura et al.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 18597-18605

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Control of axon elongation via an SDF-1α/Rho/mDia pathway in cultured cerebellar granule neurons.2003

    • Author(s)
      Arakawa 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
      2004 Final Research Report Summary
  • [Journal Article] Ca2+/CREB/CBP-dependent gene regulation : a shared mechanism critical in long-term synaptic plasticity and neuronal survival.2003

    • Author(s)
      Bito H, Takemoto-Kimura S
    • Journal Title

      Cell Calcium 34

      Pages: 425-430

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dynamic control of neuronal morphogenesis by Rho signaling.2003

    • Author(s)
      Bito H
    • Journal Title

      J.Biochem. 134

      Pages: 315-319

    • NAID

      50000316555

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 中枢神経細胞における突起形態制御機構2003

    • Author(s)
      尾藤晴彦, 荒川芳輝
    • Journal Title

      脳神経外科速報 13

      Pages: 845-850

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Control of axon elongation via an SDF-1α/Rho/mDia pathway in cultured cerebellar granule neurons.2003

    • Author(s)
      Arakawa et al.
    • 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
      2004 Final Research Report Summary
  • [Journal Article] Cat+/CREB/CBP-dependent gene regulation : a shared mechanism critical in long-term synaptic plasticity and neuronal survival.2003

    • Author(s)
      Bite H, Takemoto-Kimura S.
    • Journal Title

      Cell Calcium 34

      Pages: 425-430

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dynamic control of neuronal morphogenesis by Rho signaling.2003

    • Author(s)
      Bito H.
    • Journal Title

      J.Biochem. 134

      Pages: 315-319

    • NAID

      50000316555

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of neuritogenesis in the central nervous system2003

    • Author(s)
      Bito H, Arakawa Y.
    • Journal Title

      Communication in Neurosurgery (in Japanese) 13

      Pages: 845-850

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Takemoto-Kimura et al.: "Molecular cloning and characterization of CLICK-III /CaMKIγ, a novel membrane-anchored neuronal CaMK"J.Biol.Chem.. 278. 18597-18605 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arakawa et al.: "Control of axon elongation via an SDF-1a / Rho / mDia pathway in cultured cerebellar granule neurons."J.Cell Biol.. 161. 381-391 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bito H, Takemoto-Kimura S: "Ca2+/CREB/CBP-dependent gene regulation: a shared mechanism critical in long-term synaptic plasticity and neuronal survival."Cell Calcium. 34. 425-430 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bito H: "Dynamic control of neuronal morphogenesis by Rho signaling."J.Biochem.. 134. 315-319 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 尾藤晴彦, 荒川芳輝: "中枢神経細胞における突起形態制御機構"脳神経外科速報. 13. 845-850 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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