Mechanisms of basement membrane recognition by cell with special reference to cell adhesion-dependent signal transduction

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18370044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Osaka University
• Principal Investigator: SEKIGUCHI Kiyotoshi Osaka University, Institute for Protein Research, Professor (50187845)
• Co-Investigator(Kenkyū-buntansha): YAMADA Masashi Osaka University, Institute for Protein Research, Assistant Professor (90304055) ; FUTAKI Sugiko Osaka University, Institute for Protein Research, Assistant Professor (00403014)
• Project Period (FY): 2006 – 2007
• Keywords: basement membrane / extracellular matrix / laminin / integrin / tetraspanin / nephronectin

Research Abstract

Roles of individual subunit chains of laminins (i.e., alpha, beta and gamma chains) in integrin binding by laminins have been investigated. We demonstrated that the C-terminal region of the gamma1 and gamma2 chains, particularly the Glu residue at the third position from their C-termini, was critically involved in integrin recognition of laminins. Thus, the deletion of the Glu residue or the substitution of a Gln for the Glu residue abrogated the integrin binding activity of laminin isoforms containing either gamma1 or gamma2 chains. To extend the importance of the Glu residue within the gamma1 and gamma2 chains, we also demonstrated that the gamma3 chain that is shorter than other gamma chains and lacks the Glu residue was defective in binding to cognitive integrins. We also found that the C-terminal regions of the beta chains, particularly the C-terminal 22 amino acid residues, were involved in modulation of integrin binding affinities of laminins. Thus, the isoforms containing the beta2 chain was more potent than those containing the beta1 chain in binding to cognitive integrins, e.g., alpha3beta1. These results indicate that the C-terminal regions of both beta and gamma chains participate in the integrin binding by laminins. We also demonstrated that among the eight RGD-binding integrins, alpha8beta1 bound specifically to nephronectin.

Research Products

• [Journal Article] The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin γ chains in integrin binding by laminins. (2007)
  • Author(s): Ido, H.
  • Journal Title: The Journal of Biological Chemistry 282 Pages: 11144-11154
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Frem3, a member of the 12 CSPG repeats-containing extracellular matrix protein family, is a basement membrane protein with tissue destribu-tion patterns distinct from those of Fras 1, Frem2, and QBRICK/Frem1. (2007)
  • Author(s): Kiyozumi, D.
  • Journal Title: Matrix Biology 26 Pages: 456-462
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Regulation of mesodermal differentiation of mouse embryonic stem cells by basement membranes. (2007)
  • Author(s): Fujiwara, H.
  • Journal Title: The Journal of Biological Chemistry 282 Pages: 29701-29711
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin Y chains in integrin binding by laminins (2007)
  • Author(s): Ido, H., Nakamura, A., Kobayashi, R., Ito, S., Li, S., Futaki, S., Sekiguchi
  • Journal Title: J. Biol. Chem 282 Pages: 11144-11154
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Frem3, a member of the 12 CSPG repeats-containing extracellular matrixprotein family, is a basement membrane protein with tissue destribu-tion patterns distinct from those of Fras1, Frem2, and QBRICK/Frem1 (2007)
  • Author(s): Kiyozumi, D., Sugimoto, N., Nakano, I., Sekiguchi, K
  • Journal Title: Matrix Biol 26 Pages: 456-462
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Regulation of mesodermal differentiation of mouse embryonic stem cells by basement membranes (2007)
  • Author(s): Fujiwara, H., Hayashi, Y., Sanzen, N., Weber, C. N., Emoto, T., Futaki, S., Niwa, H., Murray, P., Edgar, D., Sekiguchi, K
  • Journal Title: J. Biol. Chem 282 Pages: 29701-29711
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Breakdown of the reciprocal stabilization of QBRICK/Frem1, Frasl, and Frem2 at the basement membrane provokes Fraser syndrome-like defects. (2006)
  • Author(s): Kiyozumi, D.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 11981-11986
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like defects (2006)
  • Author(s): Kiyozumi, D., Sugimoto, N., Sekiguchi, K
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 11981-11986
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Diversity and specificity of the adhesive interactions of cells with the basement membrane. (2007)
  • Author(s): Sekiguchi, K.
  • Organizer: XIIIth International Symposium on Basement Membranes
  • Place of Presentation: Cologne, Germany
  • Year and Date: 20070919-22
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Diversity and specificity of the adhesive interactions of cells with the basement membrane (2007)
  • Author(s): Sekiguchi, K
  • Organizer: Cologne
  • Place of Presentation: Germany
  • Year and Date: 20070919-22
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.protein.osaka-u.ac.jp/chemistry/