Customization and cellular recognition of the extracellular matrix

• Project/Area Number: 17082005
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: SEKIGUCHI Kiyotoshi Osaka University, 蛋白質研究所, 教授 (50187845)
• Co-Investigator(Kenkyū-buntansha): YAMADA Madashi 大阪大学, 蛋白質研究所, 助教 (90304055) ; FUTAKI Sugiko 大阪大学, 蛋白質研究所, 助教 (00403014) ; KIYOZUMI Daiji 大阪大学, 蛋白質研究所, 特任研究員 (70452430)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥65,000,000 (Direct Cost: ¥65,000,000); Fiscal Year 2009: ¥13,000,000 (Direct Cost: ¥13,000,000); Fiscal Year 2008: ¥13,000,000 (Direct Cost: ¥13,000,000); Fiscal Year 2007: ¥13,000,000 (Direct Cost: ¥13,000,000); Fiscal Year 2006: ¥13,000,000 (Direct Cost: ¥13,000,000); Fiscal Year 2005: ¥13,000,000 (Direct Cost: ¥13,000,000)
• Keywords: 細胞外マトリックス / 細胞接着 / 基底膜 / インテグリン / ラミニン / ネフロネクチン / テトラスパニン / 細胞外環境 / フィブロネクチン / QBRICK

Research Abstract

The critical amino acid residue defining the integrin binding site of laminins has been identified within the C-terminal region of the gamma chains. Integrin alpha8beta1 was found to specifically bind to nephronectin, a basement membrane protein containing the RGD cell-adhesive motif. Mice deficient in QBRICK, another basement membrane protein containing the RGD motif, were produced. The mice exhibit the phenotypes similar to those of Fraser syndrome, including fused eyelids and fingers, skin blisters, and kidney malformation.

Research Products

• [Journal Article] ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. (2010)
  • Author(s): Tsutsui, K., Manabe, R., Yamada, T., Nakano, I., Oguri, Y., Keene, D.R., Sengle G., Sakai, L.Y., Sekiguchi, K.
  • Journal Title: J. Biol. Chem. 285 Pages: 4870-4882
  • NAID: 120006585492
• [Journal Article] Molecular basis of the recognition of nephronectin by integrin alpha8beta1. (2009)
  • Author(s): Sato, Y., Uemura, T., Morimitsu, K., Sato-Nishiuchi, R., Manabe, R., Takagi, J., Yamada, M., Sekiguchi, K.
  • Journal Title: J. Biol. Chem. 284 Pages: 14524-14536
• [Journal Article] The carboxyl-terminal region of laminin beta chains modulates the integrin-binding affinities of laminins. (2009)
  • Author(s): Taniguchi, Y., Ido, H., Sanzen, N., Hayashi, M., Sato-Nishiuchi, R., Futaki, S., Sekiguchi, K.
  • Journal Title: J. Biol. Chem. 284 Pages: 7820-7831
• [Journal Article] Molecular basis of the recognition of nephronectin by integrinα8β1. (2009)
  • Author(s): Sato, Y., et al.
  • Journal Title: J.Biol.Chem. 284 Pages: 7820-7831
  • Peer Reviewed
• [Journal Article] ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. (2009)
  • Author(s): Tsutsui, K., et al.
  • Journal Title: J.Biol.Chem. 285 Pages: 4870-4882
  • Peer Reviewed
• [Journal Article] Anti-laminin gamma-1 pemphigoid. (2009)
  • Author(s): Dainichi, T., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 2800-2805
  • Peer Reviewed
• [Journal Article] Laminin isoforms containing the gamma3 chain are unable to bind to integrins due to the absence of the glutamic acid residue conserved in the C-terminal regions of the gamma1 and gamma2 chains. (2008)
  • Author(s): Ido, H., Ito, S., Taniguchi, Y., Hayashi, M., Sato-Nishiuchi, R., Sanzen, N., Hayashi, Y., Futaki, S., Sekiguchi, K.
  • Journal Title: J. Biol. Chem. 283 Pages: 28149-28157
• [Journal Article] Lamimn Isoforms containing. the [○!c]3 chain are unable to bind rntegrins due to the absence of the glutamic. acid residue conserved in the C-terminal regions of the γ 1 and γ 2 chains. (2008)
  • Author(s): Ido, H., et.al.
  • Journal Title: J. Biol. Chem. 283 Pages: 28149-28157
  • Peer Reviewed
• [Journal Article] Transcriptome-based systematic identification of extracellular matrix proteins (2008)
  • Author(s): Manabe, R., et.al.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 105 Pages: 12849-12854
  • Peer Reviewed
• [Journal Article] Recombinant human laminin isoforms can support the undifferentiated growth of human embryonic stem cells (2008)
  • Author(s): Miyazaki, T., et.al.
  • Journal Title: Biochem. Biophys. Res. Commun. 375 Pages: 27-32
  • Peer Reviewed
• [Journal Article] Regulation of mesodermal differentiation of mouse embryonic stem cells by basement membranes. (2007)
  • Author(s): Fujiwara, H., Hayashi, Y., Sanzen, N., Kobayashi, R., Weber, C.N., Emoto, T., Futaki, S., Niwa, H., Murray, P., Edgar, D., Sekiguchi, K.
  • Journal Title: J. Biol. Chem. 282 Pages: 29701-29711
  • NAID: 120006585496
• [Journal Article] The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin gamma chains in integrin binding by laminins. (2007)
  • Author(s): Ido, H., Nakamura, A., Kobayashi, R., Ito, S., Li, S., Futaki, S., Sekiguchi, K.
  • Journal Title: J. Biol. Chem. 282 Pages: 11144-11154
• [Journal Article] The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin γchains in integrin binding by laminins. (2007)
  • Author(s): Ido, H.
  • Journal Title: The Journal of Biological Chemistry 282 Pages: 11144-11154
  • Peer Reviewed
• [Journal Article] Frem3, a member of the 12 CSPG repeats-containing extracellular matrix protein family, is a basement membrane protein with tissue destribution patterns distinct form those of Fras 1, Frem2, and QBRICK/Freml. (2007)
  • Author(s): Kiyozumi, D.
  • Journal Title: Matrix Biology 26 Pages: 456-462
  • Peer Reviewed
• [Journal Article] Regulation of mesodermal differentiation of mouse embryonicstem cells by basement membranes. (2007)
  • Author(s): Fujiwara, H.
  • Journal Title: The Journal of Biological Chemistry. 282 Pages: 29701-29711
  • Peer Reviewed
• [Journal Article] The requirement for glutamic acid residue at the third position from the carboxyl termini of the laminin gamma chains in integrin binding by laminins. (2007)
  • Author(s): Ido, H., et al.
  • Journal Title: J. Biol. Chem. (in press)
• [Journal Article] Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like deects. (2006)
  • Author(s): Kiyozumi, D., Sugimoto, N., Sekiguchi, K.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 11981-11986
• [Journal Article] Probing the integrin-binding site within the globular domain of laminin-511 with the function-blocking monoclonal antibody 4C7. (2006)
  • Author(s): Ido, H., Harada, K., Yagi, Y., S Sekiguchi, K.
  • Journal Title: Matrix Biol. 25 Pages: 112-117
• [Journal Article] Ligand-binding specificities of laminin-binding integrins: a comprehensive survey of laminin-integrin interactions using recombinantα3β1, α6β1, α7β1 and α6β4 integrins. (2006)
  • Author(s): Nishiuchi, R., Takagi, J., Hayashi, M., Ido, H., Yagi, Y., Sanzen, N., Tsuji, T., Yamada, M., Sekiguchi, K.
  • Journal Title: Matrix Biol. 25 Pages: 189-197
• [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., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 11981-11986
• [Journal Article] A novel large-scale production system for modified basement membrane matrices using gene-swapped parietal endoderm cells. (2006)
  • Author(s): Hayashi, Y., et al.
  • Journal Title: Matrix Biol. 25 Pages: 85-88
• [Journal Article] Probing the integrin-binding site within the globular domain of laminin-511 with the function-blocking monoclonal antibody 4C7. (2006)
  • Author(s): Ido, H., et al.
  • Journal Title: Matrix Biol. 25 Pages: 112-117
• [Journal Article] Ligand-binding specificities of laminin-binding integrins : a comprehensive survey of laminin-integrin interactions using recombinant α3β1, α6β1, α7β1 and α6β4 integrins. (2006)
  • Author(s): Nishiuchi, R., et al.
  • Journal Title: Matrix Biol. 25 Pages: 189-197
• [Journal Article] Brain alpha-dystroglycan displays unique glycoepitopes and preferential binding to laminin-10/11. (2006)
  • Author(s): McDearmon, E. L., et al.
  • Journal Title: FEBS lett. 580 Pages: 3381-3385
• [Journal Article] A simplified laminin nomenclature. (2005)
  • Author(s): Aumailley, M.
  • Journal Title: Matrix Biol. 24 Pages: 326-332
• [Journal Article] Electron tomography reveals diverse conformations of integrin αIIbβ3 in the active state. (2005)
  • Author(s): Iwasaki, K.
  • Journal Title: J.Struct.Biol. 150 Pages: 259-267
• [Journal Article] Potentiation of the ligand-binding activity of integrin α3β1 via association with tetraspanin CD151. (2005)
  • Author(s): Nishiuchi, R.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 102 Pages: 1939-1944
• [Journal Article] Ligand-binding specificities of laminin-binding integrins : a comprehensive survey of laminin-integrin interactions using recombinant α3β1, α6β1, α7β1 and α6β4 integrins.
  • Author(s): Nishiuchi, R.
  • Journal Title: Matrix Biol. (in press)
• [Journal Article] Probing the integrin-binding site within the globular domain of laminin-511 with the function-blocking monoclonal antibody 4C7.
  • Author(s): Ido, H.
  • Journal Title: Matrix Biol. (in press)
• [Journal Article] A novel large-scale production system for modified basement membrane matrices using gene-swapped parietal endoderm cells.
  • Author(s): Hayashi, Y.
  • Journal Title: Matrix Biol. (in press)
• [Presentation] 基底膜分子QBRICKが持つインテグリン結合活性の生理機能評価 (2009)
  • Author(s): 浄住大慈, 他4名
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2009-10-22
• [Presentation] Customization of the basement membrane during embryonic development. (2009)
  • Author(s): Sekiguchi, K.
  • Organizer: Yokosuka Science Festa 2009 and 8th Pan-Pacific Connective Tissue Societies Symposium
  • Place of Presentation: Yokosuka, Japan
• [Presentation] Molecular basis of the recognition of nephronectin by integrinα8β1. (2009)
  • Author(s): Sato, Y., Uemura, T., Morimitsu, K., Sato-Nishiuchi, R., Manabe, R., Takagi, J., Yamada, M., Sekiguchi, K.
  • Organizer: Gordon Research Conference on Fibronectin, Integrins and Related Molecules
  • Place of Presentation: Ventura, CA, USA
• [Presentation] Customization of the basement membrane during embryonic development. (2009)
  • Author(s): Sekiguchi, K.
  • Organizer: Gordon Research Conference on Fibronectin, Integrins and Related Molecules
  • Place of Presentation: Ventura, CA, USA
• [Presentation] Molecular basis of basement membrane recognition by integrins (2008)
  • Author(s): Sekiguchi, K.
  • Organizer: Gordon Research Conference on Basement Membranes
  • Place of Presentation: Biddeford, ME, USA
  • Year and Date: 2008-06-22
• [Presentation] The carboxyl-terminal region of laminin beta chains modulates the integrin binding activity of laminins. (2008)
  • Author(s): Taniguchi, Y., Ido, H., Sanzen, N., Hayashi, M., Nakano, I., Nishiuchi, R., Futaki, S., Sekiguchi, K.
  • Organizer: Gordon Research Conference on Basement Membranes.
  • Place of Presentation: Biddeford, ME, USA
• [Presentation] Diversification of the basement membrane composition during early stages of mouse embryogenesis. (2008)
  • Author(s): Futaki, S., Nakano, I., Manabe, R., Tsutsui, K., Sanzen, N., Sado, Y., Sekiguchi, K.
  • Organizer: Gordon Research Conference on Basement Membranes.
  • Place of Presentation: Biddeford, ME, USA
• [Presentation] Construction of Mouse Basement Membrane Bodymap, an immunohistochemical image database of basement membrane proteins in mouse embryos. (2008)
  • Author(s): Tsutsui, K., Manabe, R., Sanzen, N., Nakano, I., Sado, Y., Futaki, S., Sekiguchi, K.
  • Organizer: Gordon Research Conference on Basement Membranes.
  • Place of Presentation: Biddeford, ME, USA
• [Presentation] Molecular basis of basement membrane recognition by integrins. (2008)
  • Author(s): Sekiguchi, K.
  • Organizer: Gordon Research Conference on Basement Membranes.
  • Place of Presentation: Biddeford, ME, USA
• [Presentation] Molecular basis of adhesive interactions of cells with the basement membrane. (2007)
  • Author(s): Sekiguchi, K.
  • Organizer: Glycobiology and Sphingobiology 2007.
  • Place of Presentation: Tokushima, Japan
  • Year and Date: 2007-01-03
• [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
• [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
• [Presentation] Reciprocal stabilization of Fraser syndrome-associated proteins. (2006)
  • Author(s): Kiyozumi, D., Sugimoto, N., Sekiguchi, K.
  • Organizer: American Society for Matrix Biology Biennial National Meeting.
  • Place of Presentation: Nashville, TN, USA
• [Presentation] CD151 regulates cell morphology and migration of human lung adenocarcinoma. (2006)
  • Author(s): Yamada, M., Sumida, Y., Fujibayasi, A., Sekiguchi, K.
  • Organizer: FASEB Summer Research Conference on Membrane Organisation by Tetraspanins and Small Multi-transmembrane Proteins.
  • Place of Presentation: Tucson, AZ, USA
• [Book] 再生医療・細胞組織工学のためのマトリックス生物学入門. 再生医療のための細胞生物学 (2007)
  • Author(s): 関口清俊
  • Publisher: コロナ社
• [Book] 細胞外マトリックスと増殖因子:細胞を制御するシグナル伝達の分子機構. 再生医療のための細胞生物学 (2007)
  • Author(s): 山田雅司、関口清俊
  • Publisher: コロナ社
• [Book] マトリックス組込型増殖因子とマトリックス工学. 再生医療のための細胞生物学 (2007)
  • Author(s): 眞鍋理一郎、関口清俊
  • Publisher: コロナ社
• [Book] 再生医療のための細胞生物学 (2007)
  • Author(s): 関口 清俊
  • Total Pages: 211
  • Publisher: コロナ社
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/chemistry/
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/chemistry/
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/chemistry/
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/chemistry/
• [Patent(Industrial Property Rights)] ヒト多能性幹細胞用培養基材およびその利用 (2009)
  • Inventor(s): 関口清俊、二木杉子、谿口征雅、中辻憲夫、宮崎隆道、川瀬栄八郎、末盛博文
  • Industrial Property Rights Holder: 国立大学法人大阪大学および国立大学法人京都大学
  • Filing Date: 2009-10-08