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Signaltransduction of cytoskeleton and cell movement

Research Project

Project/Area Number 12219202
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

TAKENAWA Tadaomi  The University of Tokyo, Inst. Med. Sci., Professor, 医科学研究所, 教授 (40101315)

Co-Investigator(Kenkyū-buntansha) SUETSUGU Shiro  The University of Tokyo, Inst Med.Sci.Res., Associate, 医科学研究所, 助手 (70345031)
三木 裕明  東京大学, 医科学研究所, 助教授 (80302602)
深見 希代子  東京大学, 医科学研究所, 助教授 (40181242)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥222,800,000 (Direct Cost: ¥222,800,000)
Fiscal Year 2004: ¥48,000,000 (Direct Cost: ¥48,000,000)
Fiscal Year 2003: ¥49,000,000 (Direct Cost: ¥49,000,000)
Fiscal Year 2002: ¥46,000,000 (Direct Cost: ¥46,000,000)
Fiscal Year 2001: ¥42,600,000 (Direct Cost: ¥42,600,000)
Fiscal Year 2000: ¥37,200,000 (Direct Cost: ¥37,200,000)
KeywordsActin cytoskeleton / Invasion / Metastasis / WAVE / B16 cells / lamellipodia / 癌細胞 / 細胞運動 / アクチン / WASP / 糸状突起 / 葉状突起 / 系状突起
Research Abstract

We found N-WASP and WAVE which are involved in actin polymerization at leading edge, and induce filopodia and lamellipodia formation. There are 3 types of WAVE. Among them, WAVE2 is ubiquitously expressed in a wide of tissues and plays crucial role in cell movement at leading edge.
We next prepared WAVE1 and 2 knock out mice and established mouse embryonic fibroblasts which do not have WAVE1 or WAVE2. WAVE2-deficient MEF did not induce lamellipodia formation in response to chemoatractants, and speed of cell movement was very slow. On the other hand, WAVE1-deficient MEFdidnot induce dorsal ruffles, though lamellipodia formation was still observed.
We also examined whether WAVE is involved in invasion of B16/F10 cells that are high metastatic cell lines. WAVE1 knock down did not affect the cell movement in 3 D collagen. In contrast, WAVE2 knock down inhibited cell movement, invasion in collagen gels. B16/F10 cells of WAVE2 knock down was also suppressed in metastasis to lung.

Report

(6 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (25 results)

All 2005 2004 2003 2002 Other

All Journal Article (13 results) Publications (12 results)

  • [Journal Article] Molecular mechanisms of invadopodium formation : the role of the N-WASP-Arp2/3 complex pathway and cofilin.2005

    • Author(s)
      Yamaguchi, H., Lorenz, M., Kempiak, S., Sarmiento, C., Coniglio, S., Symons, M., Segall, J., Eddy R., Miki, H., Takenawa, T., Condeefis, J.
    • Journal Title

      J.Cell Biol. 168

      Pages: 441-452

    • Related Report
      2004 Annual Research Report
  • [Journal Article] WICH, a member of WASP-interacting protein family, cross-links actin filaments.2005

    • Author(s)
      Kato M, Takenawa T.
    • Journal Title

      Biochem.Biophys.Res Commun. 328

      Pages: 1058-1066

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PtdIns(3, 4, 5)P3 binding is necessary for WAVE2-induced formation of lamellipodia.2004

    • Author(s)
      Oikawa, T., Yamaguchi, H., Itoh, T., Kato, M., Ijuin, T., Yamazaki, D., Suetsugu, S., Takenawa, T.
    • Journal Title

      Mature Cell Biol. 6

      Pages: 420-426

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ptdlns(3,4,5)P3 binding is necessary for WAVE2-induced formation of lamellipodia.2004

    • Author(s)
      Oikawa, T., Yamaguchi, H., Itoh, T., Kato, M., Ijuin, T., Yamazaki, D., Suetsugu, S., Takenawa, T.
    • Journal Title

      Nature Cell Biol. 6

      Pages: 420-426

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Arp2/3 activity is necessary for efficient formation of E-cadherin adhesive contacts.2004

    • Author(s)
      Vemra, S., Shewan, A.M., Scott, J.A., Helwani, F.M., den Elzen, N.R., Miki, Takenawa, T., Yap, AS.
    • Journal Title

      J Biol.Chem. 279

      Pages: 34062-34070

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Phospholipase C delta-type consists of three isozymes : bovine PLCdelta2 is a homologue of human/mouse PLCdelta4.2004

    • Author(s)
      Irino, Y., Cho, H., Nakamura, Y., Nakahara, M., Furutani, M., Suh, P.G., Takenawa, T., Fukami, K.
    • Journal Title

      Biochem.Biophys.Res Commun. 23

      Pages: 537-543

    • Related Report
      2004 Annual Research Report
  • [Journal Article] IRSp53/Eps8 complex is important for positive regulation of Rac and cancer cell motility/invasiveness.2004

    • Author(s)
      Funato, Y., Terabayashi, T., Suenaga, N., Seiki, M., Takenawa, T., Miki, H.
    • Journal Title

      Cancer Res. 64

      Pages: 5237-5244

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1.2004

    • Author(s)
      Suetsugu S., Tezuka T., Morimura T., Hattori M., Mikoshiba K., Yamamoto T., Takenawa T.
    • Journal Title

      Biochem J. 1-8

      Pages: 384-384

    • Related Report
      2004 Annual Research Report
  • [Journal Article] WAVE2, involved in directed cell migration, is required for caldiovascular development.2003

    • Author(s)
      Yamazaki, D., Suetsugu, S., Miki, H., Kataoka, Y., Nishikawa, S., Fujiwara, T., Yoshida, N., Takenawa, T.
    • Journal Title

      Nature 424

      Pages: 452-456

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration.2003

    • Author(s)
      Suetsugu, S., Yamazaki, D., Kurisu, S., Takenawa, T.
    • Journal Title

      Dev. Cell. 5

      Pages: 595-609

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] WAVE2, involved in directed cell migration, is required for cardiovascular development.2003

    • Author(s)
      Yamazaki, D., Suetsugu, S., Miki, H., Kataoka, Y., Nishikawa, S., Fujiwara, T., Yoshida, N., Takenawa, T.
    • Journal Title

      Nature 424

      Pages: 452-456

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sustained Activation of N-WASP through Phosphorylation is Essential for Neurite Extension.2002

    • Author(s)
      Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K., Takenawa, T
    • Journal Title

      Dev. Cell 3

      Pages: 645-658

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sustained Activation of N-WASP through Phosphorylation is Essential for Neurite Extension.2002

    • Author(s)
      Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K., Takenawa, T.
    • Journal Title

      Dev. Cell 3

      Pages: 645-658

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K., Takenawa, T.: "Sustained Activation of N-WASP through Phosphorylation Is Essential for Neurite Extension"Dev Cell. 3. 645-658 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nozumi, M., Nakagawa, H., Miki, H., Takenawa, T., Miyamoto, S.: "Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone"J Cell Sci. 116. 239-246 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ijuin, T., Takenawa, T.: "SKIP Negatively Regulates Insulin-Induced GLUT4 Translocation and Membrane Ruffle Formation"Mol Cell Biol.. 23. 1209-1220 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K., Takenawa T: "Sustained Activation of N-WASP through Phosphorylation Is Essential for Neurite Extension"Dev Cell. 3. 645-658 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nozumi, M., Nakagawa, H., Miki, H., Takenawa, T., Miyamoto, S.: "Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone"J Cell Sci. 116. 239-246 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ijuin, T., Takenawa, T.: "SKIP Negatively Regulates Insulin-Induced GLUT4 Translocation and Membrane Ruffle Formation"Mol Cell Biol.. 23. 1209-1220 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukuoka, M: "A novel N-WASP binding protein, WISH induced Arp2/3 complex activation independent of Cdc42"J. Cell Biol.. 152. 471-472 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takenawa, T: "WASP and WAVE family proteins : key molecules for rapid rearrangement of cortical actin filaments and cell movement"J. Cell Sci.. 114. 1801-1809 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suetsugu, S: "Identification of another Actin-related protein (Arp) 2/3 complex binding site in Neural Wiskott-Aldrich syndrome protein (N-WASP), that complements actin polymerization induced by the Art2/3 complex activating (VCA) domain of N-WASP"J. Biol. Chem.. 276. 33175-33181 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamaguchi,H.: "Two tandem verprolin homology domains are necessary for a strong activation of Arp2/3 complex-induced actin polvmerization and induction of microspike formation by N-WASP"Proc.Natl.Acad.Sci.USA.. 97. 12631-12636 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yang,C.: "Profilin enhances Cdc42-induced nucleation of actin polymerization."J.Cell Biol.. 150. 1001-1012 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miki,H.: "IRSp53 is an essential intermediate in the regulation of membrance ruffling by Rac and WAVE."Nature. 408. 732-735 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2018-03-28  

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