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Dynamic reorganization of cytoskeletion by WASP family proteins

Research Project

Project/Area Number 12307003
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

TAKENAWA Tadaomi  Institute of Medical Science, Professor, 医科学研究所, 教授 (40101315)

Co-Investigator(Kenkyū-buntansha) ITOH Toshiki  Institute of Medical Science, Associate Professor, 医科学研究所, 助手 (30313092)
FUKAMI Kiyoko  Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (40181242)
三木 裕明  東京大学, 医科学研究所, 助手 (80302602)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥40,620,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2002: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2001: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2000: ¥20,600,000 (Direct Cost: ¥20,600,000)
Keywordsactin / cell movement / WASP / WAVE / cytoskeleton / 神経突起 / N-WASP / チロシンキナーゼ / ユビキチン化
Research Abstract

It is already well known that a variety of cells rearrange cytoskeleton, prepare for cell division, and stimulate motility and migration in response to various stimuli. The directed migration of cells is one of fundamental phenomena of life, including migration toward inflammatory sites, and invasion and metastasis of cancer cells.
We found WASP and WAVE proteins which are related to cytoskeleton reorganization and cell migration. All these proteins have VCA regions at C-terminal area in which V region binds actin and CA region binds Arp2/3 complex. As a result, these proteins nucleate actin filaments and enhance actin polymerization. On the other hand, at N-terminal area, there are regions to which regulatory molecules bind. N-WASP binds several molecules such as WIP, WISH, Cdc42 and PIP2, and WAVE binds IRSp53, followed by the exposure of VCA region of these proteins. Consequently, these proteins bind to Arp2/3 complex and polymerize actin filaments. Finally, N-WASP which is located downstream of Cdc42 induces filopodia formation. WAVE which is located downstream of Rac induces lamellipodia formation. These proteins are present at the leading edge of moving cells and generate driving force.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Yamaguchi, H., Miki, H., Takenawa, T: "Neural Wiskott-Aldrich Syndrome Protein is involved in hepatocyte growth factor-induced migration, invasion, and tuboligenesis of epithelial cells"Cancer Res.. 62. 2503-2509 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suetsugu, S., Hattori, M., Mild, 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Otsuki, M., Itoh, T., Takenawa, T.: "N-WASP is recruited to rafts and associates with wndophilin A in response to EGF"J. Biol. Chem.. 278. 6461-6469 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ijuin, T., Takenawa T.: "SKIP Negatively Regulates Insulin-Induced GLUT4 Translocation and Membrane Ruffle Formation"Mol. Cell. Biol.. 23. 1209-1220 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaguchi,H., Miki,H., Takenawa,T.: "Neural Wiskott-Aldrich Syndrome Protein is involved in hepatocyte growth factor-induced migration, invasion, and tuboligenesis of epithelial cells"Cancer Res.. 62. 2503-2509 (2002)

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

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Otsuki,M., Itoh,T., Takenawa,T.: "N-WASP is recruited to rafts and associates with wndophilin A in response to EGF"J.Biol.Chem.. 278. 6461-6469 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ijuin,T., Takenawa,T.: "SKIP Negatively Regulates Insulim-Induced GLUT4 Translocation and Membrane Ruffle Formation"Mol.Cell.Biol. 23. 1209-1220 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 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
      2002 Annual Research Report
  • [Publications] Abe, T., Kato, M., Miki, H., Takenawa, T., Endo, T.: "Small GTPase Tc10 and its homologue RhoT induce N-WASP mediated long process formation and neurite outgrowth"J. Cell. Sci. 116. 155-168 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Otsuki, M., Itoh, T., Takenawa, T.: "N-WASP is recruited to rafts and associates with wndophilin A in response to EGF"J. Biol. Chem.. 278. 6461-6469 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Martinez-Quiles, N.: "N.WIP regulates N-WASP-mediated actin polymerization and filopodium formation"Nature Cell Biol. 3. 484-491 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itoh, T: "The Epsin N-terminal homology (ENTH) domain : a Phosphatidylinositol 4, 5-bisphosphate binding domain essential for endocytosis"Science. 291. 1047-1051 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suetsugu, S: "Requirement of the basic region of N-WASP/WAVE2 for actin-based motility"Biochem. Biophys. Res. Commun. 282. 739-744 (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 polymerization and induction of microsoike 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-indued 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: 2016-04-21  

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