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Molecular Mechanism in Regulation of Neuronal Dendritic Morphology

Research Project

Project/Area Number 07458203
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionGunma University School of Medicine

Principal Investigator

SHIRAO Tomoaki  Neurobiology and Behavior, Gunma Univ Sch.of Med.Prof., 医学部・附属行動医学研究施設, 教授 (20171043)

Co-Investigator(Kenkyū-buntansha) KURBARA Hisashi  Neurobiology and Behavior, Gunma Univ Sch.of Med.Instr., 医学部・附属行動医学研究施設, 助手 (20008387)
HAYASHI Kensuke  Neurobiology and Behavior, Gunma Univ Sch.of Med.Instr., 医学部・附属行動医学研究施設, 助手 (50218567)
田中 聡一  群馬大学, 医学部, 助手 (20272247)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywordsdrebrin / dendritic spine / actin filament / myosin / neuronal development / Process formation / ドレブリン / スパイル / アクチン / 神経細胞 / 樹状突起
Research Abstract

(1) In order to find out the relationships between drebrin and other actin associated proteins, drebrin, myosin, actin, toropomyosin, alpha-actinin, caldeson and gelsoin were purified, and various co-purification study with actin filament have been done. Drebrin binds to actin filaments at a stoichiometry of 1 : 5, with a dissociation constant (Kd) of 1.2x10^<-7>M.Drebrin does not exhibit any actin-nucleating, actin-severing or actin-capping activity, nor does it crosslink actin filaments. Drebrin did not affect the activity of gelsolin or actin binding activity of caldesmon and filamin, but strongly inhibited the actin binding activity of tropomyosin, and the actin binding and actin cross-linking activities of alpha-actinin and fascin. Drebrin has an inhibitory effect on actomyosin interation and might be an actin-linked regulatory protein of actomyosin interaction within neurons.
(2) The morphological changes of dendritic spines of neurons have been postulated to participate in the expression of synaptic plasticity. We have examined the molecular mechanisms responsible for the changes in spine morphology, focusing on a protein that binds to actin filaments, drebrin, that is concentrated in neurons. We found that adult-type drebrin is localized in the dendritic spines in the forebrain of the rat, where it binds to the cytoskeleton of the spine. The drebrin-containing cytoskeleton consisted of drebrin, actin, myosin and gelsolin. In vitro, drebrin inhibited the movement of actin filaments on a glass surface that had been coated with myosin and reduced the actin-dependent ATPase activity of myosin. These results suggest that drebrin modulates the acto-myosin activity within spines and plays a role in the structure-based plasticity of synapses.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] T.Shirao: "The roles of microfilament-associated proteins,drebrins in brain morphogenensis" J.Biochem. 117. 231-236 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Kobayashi: "K252a,a potent inhibitor of protein kinases,inhibits the migration" Dev.Brain Res.90. 122-128 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Harigaya: "Disappearance of actin-binding protein,drebrin,from hippocampal sysnapses" J.Neurosci Res.43. 87-92 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Ikeda.: "Stabilization of adhesion playues by the expression of drebrin" Dev.Brain Res.91. 227-236 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Sasaki: "Inhibition by drebrin of the actin-binding activity of brain fascin." J.Neurochem.66. 980-988 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Hayashi: "Modulatory role of drebrin on the cytoskeleton within dendritic spines" J.Neurosci.15. 7161-7170 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tomoaki Shirao: ""The roles of microfilament-associatedproteins, drebrins in brain morphogenesis : A Review"." J.Biochem.117. 231-236 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Keiro Ikeda, Tomoaki Shirao, Masahiro Toda, Hideo Asada, Shigeo Toya and Keiichi Uyemura: ""Effect of neuron-specific actin-bindingprotein, drebrin A,on cell-substratumadhesion."" Neurosci.Lett.194. 197-200 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nobuaki Nakatsubo, Okio Arai and Tomoaki Shirao: ""Identification of the newly generatedneruons of canaries during adulthood"" Dokyo Journal of Medical Sciences. 22. 65-72 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Kobayashi, K Isa, K.Hayashi, K.K.Inoue, K Uyemura and T.Shirao: ""K252a, a potent inhibitor of protein kinases, inhibits the migration of cerebellargranule cells in vitro"" Dev.Brain Res.90. 122-128 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Harigaya, M.Shoji, T.Shirao and S.Hirai: ""Disappearance of actin-bindingprotein, drebrin, from hippocampal sysnapses in Alzheimer's Disease."" J.Neurosci.Res.43. 87-92 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Ikeda, P.A.Kaub, H.Asada, K.Uyemura, S.Toya, and T.Shirao: ""Stabilization of adhesion plaques by the expression of drebrin A in fibroblasts."" Dev.Brain Res.91. 227-236 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Sasaki, K.Hayashi, T.Shirao, R.Ishikawa and K Kohama: ""Inhibition by drebrinof the actin-binding activity of brain fascin, a protein localized in filopodia of growth cones."" J.Neurochem.66. 980-988 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Hayashi, R.Ishikawa, Y Li-Hong, X.HE,K.Takata, K.Kohama and T.Shirao: ""Modulatory role of drebrin on the cytoskeleton within dendritic spines in rat cerebralcortex."" J.Neurosci.15. 7161-7170 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Shirao: "The roles of microfilament associated proteins,drebrins in brain morphogenesis" J.Biochem. 117. 231-236 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Kobayashi: "K252a,a potent inhibltor of protein kinases,inhibits the migration" Dev.Brain Res.90. 122-128 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Harigaya: "Disappearance of actin-binding protein,drebrin,from hippocampal sysnapses" J. Neurosci Res.43. 87-92 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Ikeda: "Stabilization of adhesion plagues by the expression of drebrin" Dev. Brain Res.91. 227-236 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Sasaki: "Inhibition by drebrin of the actin-binding activity of brain fascin." J. Neurochem.66. 980-988 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Hayashi: "Modulatory role of drebrin on the cytoskeleton within dendritic spines" J. Neurosci.15. 7161-7170 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K. Ikeda: "Stabilization of adhesion plagues by the expression of drebrin A in fibroblasts" Developmental Brain Research.

    • Related Report
      1995 Annual Research Report
  • [Publications] Y. Sasaki: "Inhibition by drebrin of the actin-binding activity of brain fuscin, a protein localized in filopodia." J. Neurochemistry.

    • Related Report
      1995 Annual Research Report
  • [Publications] 田中聡一: "培養小脳顆粒細胞移動抑制の免疫組織化学的解析" 神経組織の成長,再生,移植. 6. 33-34 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 田中聡一: "K252aによる培養小脳顆粒細胞移動抑制のメカニズム" 神経化学. 34. 74-45 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 佐々木洋: "脳ファシンの解析:アクチン線維結合束化能に及ぼすドレブリンの影響" 神経化学. 34. 292-293 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 池田圭朗: "アクチン結合蛋白ドレブリンAによる細胞骨格及び細胞接着の変化" 神経化学. 34. 294-295 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2017-10-10  

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