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Protein-protein interactions underlying the formation of microdomains on the cell surface

Research Project

Project/Area Number 14370042
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HATA Yutaka  Tokyo Medical and Dental University, Dept. Med. Biochem., Professor, 大学院・医歯学総合研究科, 教授 (80313237)

Co-Investigator(Kenkyū-buntansha) 西村 渉  東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (00334433)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
KeywordsEpithelial junctions / Synapses / Membrane-associated guanylate kinases / Cell adhesion / シナプス
Research Abstract

Multicellular organisms have various cell junctions and the structure termed a raft on the cell surface. These microdomains are composed of unique sets of proteins including receptors, cell adhesion molecules, cytoskeleton adaptor proteins, and signaling molecules. These components are organized as a functional complex through sequential protein-protein interactions. Because the disruption of cell junctions and other microdomains is implicated in various diseases, it is important to clarify how each protein is assembled into the complex.
We have studied a synaptic membrane-associated guanylate kinase (MAGUK) protein named S-SCAM. We previously reported that S-SCAM binds β-catenin. In this study, we have identified Axin, which regulates β-catenin degradation, as a binding partner of S-SCAM. We have also found that S-SCAM induces the synaptic accumulation of a cell adhesion molecule named neuroligin, and that neuroligin subsequently recruits another MAGUK protein, PSD-95, to synapses. Moreover, we have studied how SAPAP, a cytoskeleton adaptor protein that interacts with both of S-SCAM and PSD-95, is targeted to synapses.
A non-neuronal isoform of S-SCAM is named MIAGI-1 that is localized at tight junctions in epithelial cells. We have searched for MAGI-1-interacting proteins and discovered two novel molecules, JAM4 and Carom. JAM4 is a cell adhesion molecule that belongs to the immunoglobulin superfamily and involved in the regulation of paracellular permeability. Carom is a cytoskeleton adaptor protein. Carom binds to MAGI-1 in vitro. However, in polarized epithelial cells, Carom is not concentrated at tight junctions, is separate from MAGI-1, and interacts with CASK, which also belongs to MAGUK family of proteins. This finding suggests that protein-protein interactions are not stable but change during the establishment of cell polarity.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Shirasawa, M., et al.: "Receptor for advanced glycation end-products is a marker for type I lung alveolar cells."Genes to Cells. 9(2). 165-174 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohno, H., et al.: "Carom : a novel membrane-associated guanylate kinase-interacting protein with two SH3 domains."Oncogene. 22(52). 8422-8431 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tajima, M., et al.: "Roles of immunoglobulin-like loops of injuctional cell adhesion molecule 4; involvement in the subcellular localization and the cell adhesion."Genes to Cells. 8(9). 759-768 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirabayashi, S., et al.: "JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1."Mol.Cell.Biol.. 23(12). 4267-4282 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yao, I.et al.: "Synaptic localization of SAPAP1, a synaptic membrane-associated protein."Genes to Cells. 8(2). 121-129 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirabayashi, S., et al.: "Synaptic scaffolding molecule interacts with Axin."J.Neurochem.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirabayashi, S., et al.: "Synaptic scaffolding molecule interacts with Axin."J. Neurochem.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shirasawa, M., et al.: "Receptor for advanced glycation end-products is a marker for type I lung alveolar cells."Genes Cells. 9(2). 165-174 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohno, H., et al.: "Carom: a novel membrane-associated guanylate kinase-interacting protein with SH3 domains."Oncogene. 22(52). 8422-8431 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tajima, M., et al.: "Roles of immunoglobulin-like loops of junctional cell adhesion molecule 4; involvement in the subcellular localization and the cell adhesion."Genes Cells. 8(9). 759-758 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirabayashi, S., et al.: "JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1."Mol. Cell. Biol.. 23(12). 4267-4282 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yao, I., et al.: "Synaptic localization of SAPAP 1, a synaptic membrane-associated protein."Genes Cels. 8(2). 121-129 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohno, H., et al.: "Localization of p0071-interacting proteins, PAPIN and ERBIN."Oncogene. 21(46). 7042-7049 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yao, I., et al.: "Synaptic and nuclear localization of brain-enriched guanylate kinase -associated protein."J. Neurosci.. 22(13). 5354-5364

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shirasawa, M., et al.: "Receptor for advanced glycation end-products is a marker for type I lung alveolar cells."Genes to Cells. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohno, H., et al.: "Carom : a novel membrane-associated guanylate kinase-interacting protein with two SH3 domains."Oncogene. 22(52). 8422-8431 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tajima, M., et al.: "Roles of immunoglobulin-like loops of junctional cell adhesion molecule 4 ; involvement in the subcellular localization and the cell adhesion."Genes to Cells. 8(9). 759-768 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirabayashi, S., et al.: "JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1."Mol.Cell.Biol.. 23(12). 4267-4282 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yao, I.et al.: "Synaptic localization of SAPAP1, a synaptic membrane-associated protein."Genes to Cells. 8(2). 121-129 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishimura, W., et al.: "Interaction of synaptic scaffolding molecule (S-SCAM) and β-catenin"Journal of Neuroscience. 22. 757-765 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iida, J. et al.: "Synaptic localization of membrane-associated guanylate kinase-interacting protein mediated by the pleckstrin homology domain"European Journal of Neurscience. 15. 1493-1498 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohno, H., et al.: "Localization of p0071-interacting proteins, PAPIN and ERBIN"Oncogene. 21. 7042-7049 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yao, I., et al.: "Synaptic and nuclear localization of brain-enriched guanylate kinase-associated protein"Journal of Neuroscience. 22. 5354-5364 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirabayashi, S., et al.: "C2PA is a nuclear protein implicated in the heat shock response"Journal of Cellular Biochemistry. 87. 65-74 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yao, I., et al.: "Synaptic localization of SAPAP1, a synaptic membrane-associated protein"Genes to Cells. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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