Elucidation of acute actin polymerization signaling using single molecule imaging of filament end factors

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390075
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Naoki Kyoto University, 医学研究科, 准教授 (80303816)
• Project Period (FY): 2007 – 2008
• Keywords: 細胞 / 組織 / 一分子計測 / 生体分子 / ナノバイオ

Research Abstract

多くの生命機能は細胞の形態変化と密接に連関し、動的なアクチン重合が多く関わっている。まず、アクチン脱重合因子AIP1 の単分子可視化により、細胞伸展部で毎秒280アクチン分子長の線維に1回線維が切断されることを見出した. これは主要なアクチン重合端形成機構と考えられたArp2/3複合体による重合核形成の15倍の高頻度である. また, フォルミン蛋白質mDia1がアクチン単量体増加にトリガーされ, プロセッシブに線維伸長させるアクチン線維修復機構を見出した. 線維崩壊から迅速にアクチン再重合させるフィードバック機構が明らかとなった。

Research Products

• [Journal Article] Cdc42 and Rac family GTPases regulate mode and speed but not direction of primary fibroblast migration during PDGF dependent chemotaxis (2009)
  • Author(s): Monypenny, J., Zicha, D., Higashida, C., Oceguera-Yanez, F., Narumiya, S. and Watanabe, N.
  • Journal Title: Mol.Cell. Biol. 29 Pages: 2730-2747
• [Journal Article] An order of magnitude faster AIP1 associated actin disruption than nucleation by the Arp2/3 complex in lamellipodia (2009)
  • Author(s): Tsuji, T., Miyoshi, T., Higashida, C.,Narumiya, S. Watanabe, N.
  • Journal Title: PLoS ONE 4 Pages: e4921
• [Journal Article] Imatinib mesylate (STI571)-induced cell edge translocation of kinase active and kinase defective Abelson kinase : requirements of myristoylation and src homology 3 domain (2009)
  • Author(s): Fujita, A., Shishido, T., Yuan, Y., Inamoto, E., Narumiya, S. and Watanabe, N.
  • Journal Title: Mol. Pharmacol 75 Pages: 75-84
• [Journal Article] G-actin regulates rapid induction of actin nucleation by mDia1 to restore cellular actin polymers (2008)
  • Author(s): Higashida, C., Suetsugu, S., Tsuji, T., Monypenny, J., Narumiya, S. Watanabe, N.
  • Journal Title: J. Cell Sci. 121 Pages: 3403-3412
• [Journal Article] Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon utgrowth (2008)
  • Author(s): Shimada T, Toriyama M, Uemura1 K, Kamiguchi H, Sugiura T, Watanabe N, *Inagaki N.
  • Journal Title: J. Cell Biol. 181 Pages: 817-829
• [Journal Article] mDia2 induces the actin scaffold for the contractile ring and stabilizes its position during cytokinesis in NIH 3T3 cells (2008)
  • Author(s): Watanabe S, Ando Y, Yasuda S, Hosoya H, Watanabe N, Ishizaki T, *Narumiya S.
  • Journal Title: Mol.Biol. Cell 19 Pages: 2328-2338
• [Presentation] STI571 induced cell edge translocation of abl kinase (2009)
  • Author(s): Yuan Y., Fujita A., Shishido T., Narumiya S., Watanabe N
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜(speaker)
  • Year and Date: 2009-03-18
• [Presentation] Rapid actin polymer restoration mechanism by mDia1 and othe actin nucleators regulated by concentration fluctuation of G-actin (2008)
  • Author(s): Higashida C., Suetsugu S., Narumiya S., Watanabe N.
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会シンポジウム(企画・主催)
  • Place of Presentation: 神戸(speaker)
  • Year and Date: 2008-12-11
• [Presentation] A paradoxical effect of actin monomer inhibitors to increase drug free G actin in cells : an unexpected role of G actin revealed by pharmacokinetic simulation (2008)
  • Author(s): Watanabe N., Higashida C.
  • Organizer: The Uehara Memorial Foundation Symposium 2008.; Systems Biology : the Challenge of Complexity
  • Place of Presentation: 東京
  • Year and Date: 2008-07-01
• [Presentation] Challenging frequent filament severing annealing hypothesis by single molecule imaging of AIP1, a cofilin dependent actin barbed end interacting protein (2007)
  • Author(s): Watanabe N., Higashida C., Tsuji T.
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大8会合同大会ワークショップ(企画・主催)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Book] A possible role of homeostasis between monomeric and filamentous actin in filament nucleation reveald by pharmacokinetic modeling (2008)
  • Author(s): Watanabe N. and Higashida C.
  • Total Pages: 143-149
  • Publisher: Systems Biology The Challenge of Complexity. Springer