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Analysis of protein tyrosine phosphorylation signal, which regulates synaptic function.

Research Project

Project/Area Number 16500236
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OHNISHI Hiroshi  GUNMA UNIVERSITY, INSTITUTE FOR MOLECULAR AND CELLULAR REGULATION, ASSOCIATE PROFESSOR, 生体調節研究所, 助教授 (70334125)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsProtein tyrosine phosphorylation / Intercellular communication / Axon / Dendrite / Neuronal network / Neuronal morphology / SHPS-1 / CD47 / 神経栄養因子 / 神経軸策 / 神経シナプス / 神経回路網
Research Abstract

SHPS-1 (SHP substrate-1) is a member of immunoglobulin superfamily membrane proteins. Cytoplasmic region of SHPS-1 contains tyrosine residues, which are phosphorylated and binds to a cytplasmic protein tyrosine phosphatase, SHP-2. SHPS-1 is highly expressed in the brain, and thought to have an important function to regulate tyrosine phosphorylation signal in the central nervous system. Extracellular region of SHPS-1 specifically interacts with its physiological ligand, CD47. CD47 is also an immunoglobulin superfamily membrane protein. This interaction between CD47 and SHPS-1 constitutes an intercellular communication system (the CD47-SHPS-1 system). In this research, we analyzed expression patterns of these two molecules by using primary cultured hippocampal neurons, and we found that SHPS-1 and CD47 were localized in a different manner; the former was predominantly on axons and the latter on dendrites, respectively. These results suggest that the CD47-SHPS-1 system acts as a directional intercellular signaling system at the interaction sites between dendrites and axons. We have also investigated the function of the CD47-SHPS-1 system in cultured neurons. We found that forced expression of CD47 promoted neurite formation. We also found that an Fc fusion protein containing the extracellular region of SHPS-1 induced filopodium formation in these neurons. Furthermore, exogenously expressed SHPS-1 and CD47 were markedly accumulated at the enlarged contact sites of axon and dendrite, each of which was derived from neurons transfected separately. All our findings suggest the CD47-SHPS-1 system regulates morphological change of neurons at their contact site, thereby regulates neuronal network formation. We are planning to further investigate the physiological importance of the CD47-SHPS-1 system in the regulation of neuronal function.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004

All Journal Article (22 results) Book (5 results)

  • [Journal Article] SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages.2006

    • Author(s)
      Ishikawa-Sekigami, T. et al.
    • Journal Title

      Blood 107巻・1号

      Pages: 341-348

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Crystallization and preliminary X-ray analysis of rat SHPS-1.2006

    • Author(s)
      Nagata, A. et al.
    • Journal Title

      Acta Crystallographica. Section F, Structural Biology and Crystallization Communications 62巻・3号

      Pages: 189-191

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages.2006

    • Author(s)
      Ishikawa-Sekigami, T. et al.
    • Journal Title

      Blood 107

      Pages: 341-348

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Crystallization and preliminary X-ray analysis of rat SHPS-1.2006

    • Author(s)
      Nagata, A. et al.
    • Journal Title

      Acta Crystallograph.Sect.F Struct.Biol.Cryst.Commun. 62(Pt3)

      Pages: 189-191

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential localization of SH2 domain-containing protein tyrosine phosphatase substrate-1 and CD47 and its molecular mechanism in cultured hipnocampal neurons2005

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

      The Journal of Neuroscience 25巻・10号

      Pages: 2702-2711

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system.2005

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

      The Journal of Immunology 174巻・4号

      Pages: 2004-2011

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Differential localization of SH2 domain-containing protein tyrosine phosphatase substrate-1 and CD47 and its molecular mechanism in cultured hippocampal neurons.2005

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

      J.Neurosci. 25

      Pages: 2702-2711

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system.2005

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

      J.Immunol. 174

      Pages: 2004-2011

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential localization of SH2 domain-containing protein tyrosine phosphatase substrate-1 and CD47 and its molecular mechanism in cultured hippocampal neurons.2005

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

      The Journal of Neuroscience 25巻・10号

      Pages: 2702-2711

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis.2004

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

      Nature 424巻・6984号

      Pages: 758-763

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ectodomain shedding of SHPS-1 and its role in regulation of cell migration.2004

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

      The Journal of Biological Chemistry 279巻・27号

      Pages: 27878-27887

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive regulation of phagocytosis by SIRPβ and its signaling mechanism in macrophages.2004

    • Author(s)
      Hayashi, A. et al.
    • Journal Title

      The Journal of Biological Chemistry 279巻・28号

      Pages: 29450-29460

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Promotion of neurite and filopodium formation by CD47 : Roles of integrins, Rac, and Cdc42.2004

    • Author(s)
      Miyashita, M. et al.
    • Journal Title

      Molecular Biology of the Cell 15巻・8号

      Pages: 3950-3963

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis.2004

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

      Nature 424

      Pages: 758-763

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ectodomain shedding of SHPS-1 and its role in regulation of cell migration.2004

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

      J.Biol.Chem. 279

      Pages: 27878-27887

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive regulation of phagocytosis by SIRPβ and its signaling mechanism in macrophages.2004

    • Author(s)
      Hayashi, A. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 29450-29460

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Promotion of neurite and filopodium formation by CD47 : Roles of integrins, Rac, and Cdc42.2004

    • Author(s)
      Miyashita, M. et al.
    • Journal Title

      Mol.Biol.Cell 15

      Pages: 3950-3963

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ectodomain shedding of SHPS-1 and its role in regulation of cell migration2004

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

      The Journal of Biological Chemistry 279巻・27号

      Pages: 27878-27887

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Promotion of neurite and filopodium formation by CD47 : Roles of integrins, Rac, and Cdc422004

    • Author(s)
      Miyashita, M. et al.
    • Journal Title

      Molecular Biology of the Cell 15巻・8号

      Pages: 3950-3963

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Positive regulation of phagocytosis by SIRPbeta and its signaling mechanism in macrophages2004

    • Author(s)
      Hayashi, A. et al.
    • Journal Title

      The Journal of Biological Chemistry 279巻・28号

      Pages: 29450-29460

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis2004

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

      Nature 428巻・6984号

      Pages: 758-763

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS-1 in response to endoplasmic retivulum stress2004

    • Author(s)
      Murai-Takebe, R. et al.
    • Journal Title

      The Journal of Biological Chemistry 279巻・12号

      Pages: 11616-11625

    • Related Report
      2004 Annual Research Report
  • [Book] ブレインサイエンス・レビュー20052005

    • Author(s)
      大西浩史 ら
    • Total Pages
      263
    • Publisher
      クバプロ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 生化学77巻10号2005

    • Author(s)
      的崎 尚 ら
    • Total Pages
      121
    • Publisher
      日本生化学会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 神経化学44巻4号2005

    • Author(s)
      大西浩史 ら
    • Total Pages
      75
    • Publisher
      日本神経化学会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] タンパク質科学イラストレイテッド2005

    • Author(s)
      大西浩史 ら
    • Total Pages
      332
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 細胞工学 vol.23 No.52004

    • Author(s)
      大西浩史 ら
    • Total Pages
      96
    • Publisher
      秀潤社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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