Molecular mechanisms underlying regulation of epithelial cell functions by laminins through integrin a3b1-based protein complex

• Project/Area Number: 19570104
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Osaka University
• Principal Investigator: YAMADA Masashi Osaka University, 蛋白質研究所, 助教 (90304055)
• Co-Investigator(Kenkyū-buntansha): SEKIGUCHI Kiyotoshi 大阪大学, 蛋白質研究所, 教授 (50187845)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞外マトリックス / 基底膜 / ラミニン / インテグリン / テトラスパニン / 細胞内シグナル / CD151

Research Abstract

インテグリンα3β1と強固に結合しているテトラスパニンCD151 が、インテグリンα3β1 を介するラミニン511接着により惹起されるp130Cas, FAKおよびパキシリンのチロシンリン酸化シグナルを正に制御することを明らかにした。さらに、CD151は、細胞内シグナルの調節に加え、インテグリンα3β1を介した接着強度を増強することにより上皮細胞の形態や遊走の制御に関与することを見出した。CD151はEC1, EC2と呼ばれる2つの細胞外領域を持ち、その内、EC2がインテグリンα3との相互作用に働いていることがわかっている。我々は、10種類の抗CD151モノクローナル抗体のエピトープ・マッピングを行うことによりCD151とインテグリンα3β1の結合様式の解明を目指した。その結果、CD151のEC2上に存在する6アミノ酸残基からなる配列がインテグリンα3β1との結合に関与していることを新たに見出した

Research Products

• [Journal Article] Molecular basis of the recognition of nephronectin by integrin α8β1 (2009)
  • Author(s): Sato, Y., Uemura, T., Morimitsu, K., Sato-Nishiuchi, R., Manabe. R. I., Takagi, J., Yamada, M., and Sekiguchi, K.
  • Journal Title: J. Biol. Chem (in press)
  • NAID: 120006585493
  • Peer Reviewed
• [Journal Article] Probing the interaction of tetraspanin CD151 with integrin α3β1 using a panel of monoclonal antibodies with distinct reactivities toward the CD151-integrin α3β1 complex (2008)
  • Author(s): Yamada, M., Tamura, Y., Sanzen, N., Sato-Nishiuchi, R., Hasegawa, H., Ashman, L.K., Rubinstein, E., Yanez-Mo, M., Sanchez-Madrid, F., and Sekiguchi K.
  • Journal Title: Biochem J 415 Pages: 417-427
  • Peer Reviewed
• [Journal Article] The tetraspanin CD151 regulates cell morphology and intracellular signaling on laminin-511 (2008)
  • Author(s): Yamada, M., Sumida, Y., Fujibayashi, A., Fukaguchi, K., Sanzen, N., Nishiuchi, R., and Sekiguchi, K.
  • Journal Title: FEBS J. 275 Pages: 3335-3351
  • Peer Reviewed
• [Journal Article] Human RME-8 is involved in membrane trafficking through early endosomes (2008)
  • Author(s): Fujibayashi A., Taguchi, T., Misaki, R.,Ohtani, M., Dohmae, N., Takio, K., Yamada, M., Gu, J., Yamakami, M., Fukuda, M., Waguri, S., Uchiyama, Y., Yoshimori, T., and Sekiguchi, K.
  • Journal Title: Cell Struct. Funct 33 Pages: 35-50
  • NAID: 130004053865
  • Peer Reviewed
• [Journal Article] Probing the interaction of tetraspanin CD151 with integrin α3β1 using a panel of monoclonal antibodies with distinct reactivities toward the CD151-integnn α3β1 complex (2008)
  • Author(s): Yamada, M.
  • Journal Title: Biochemical Journal 415 Pages: 417-427
  • Peer Reviewed
• [Journal Article] The tetraspanin CD151 regulates cell morphology and intracellular signaling on laminin-5 11 (2008)
  • Author(s): Yamada, M.
  • Journal Title: FEBS Journal 275 Pages: 3335-3351
  • Peer Reviewed
• [Presentation] Tetraspanin CD151 regulates cellmorphology, motility and signaling on laminin-511 (2008)
  • Author(s): Masashi Yamada, Yasuhiro Sumida, Akemi Fujibayashi, Kiyomitsu Fukaguchi, Noriko Sanzen, Ryoko Nishiuchi and Kiyotoshi Sekiguchi
  • Organizer: 日本細胞生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-01
• [Presentation] Tetraspanin CD151 regulates cell morphology, raotility and signaling on laminin-5 1 1 (2008)
  • Author(s): 山田 雅司
  • Organizer: 日本細胞生物学会大会
  • Place of Presentation: 横 浜
  • Year and Date: 2008-07-01
• [Presentation] Probing the interaction of tetraspanin CD151 with integrin α3β1 through epitope mapping of anti-CD151 monoclonal antibodies (2008)
  • Author(s): Masashi Yamada, Yumiko Tamura, Noriko Sanzen, Ryoko Nishiuchi, Hitoshi Hasegawa, Leonie K. Ashman, Eric Rubinstein, Maria Yanez-Mo, Francisco Sanchez-Madrid, and Kiyotoshi Sekiguchi,
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: New Haven, CT, USA
  • Year and Date: 2008-06-23
• [Presentation] Probing the interaction of tetraspanin CD151 with integrin alpha3beta l through epitope mapping of anti-CD151monoclonal antibodies (2008)
  • Author(s): Yamada, M.
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: New Haven, CT, USA
  • Year and Date: 2008-06-23
• [Presentation] Classification of anti-tetraspanin CD151 monoclonal antibodies based on their ability to dissociate the CD151-integrin α3β1 complex and their epitope mapping (2007)
  • Author(s): Masashi Yamada, Yumiko Tamura, Noriko Sanzen, Ryoko Nishiuchi and Kiyotoshi Sekiguchi
  • Organizer: 日本分子生物学会・日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] ネフロネクチンのドメイン機能の解析 (2007)
  • Author(s): 佐藤祐哉、上村俊人、盛満圭介、杉浦信夫、木全弘治、長田亜樹、眞鍋理一郎、高木淳一、山田雅司、関口清俊
  • Organizer: 日本分子生物学会・日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Ryoko Nishiuchi and Kiyotoshi Sekiguchi, Tetraspanin CD151 regulates morphology (2007)
  • Author(s): Masashi Yamada, Yasuhiro Sumida, Akemi Fujibayashi, Kiyomitsu Fukaguchi, Noriko Sanzen
  • Organizer: motility, and intracellular signaling of A549 human lung adenocarcinoma cells on laminin-10. The American Society for Cell Biology
  • Place of Presentation: Washington, D.C., USA
  • Year and Date: 2007-12-03
• [Presentation] Tetraspanin CD151 regulates morphology, motility, and intracellular signaling of A549 human lung adenocarcinoma cells on laminin-10 (2007)
  • Author(s): 山田 雅司
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: ワシントンDC,アメリカ合衆国
  • Year and Date: 2007-12-03
• [Book] 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] 再生医療のための細胞生物学 (2007)
  • Author(s): 関口 清俊
  • Total Pages: 208
  • 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/