Signaltransduction of cytoskeleton and cell movement

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 12219202
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The 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)
• Project Period (FY): 2000 – 2004
• Keywords: Actin cytoskeleton / Invasion / Metastasis / WAVE / B16 cells / lamellipodia

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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