Elucidation of the spatio-temporal regulated formation mechanism of cellular actin-based structures.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24770175
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Tohoku University
• Principal Investigator: MIZUNO Hiroaki 東北大学, 生命科学研究科, 助教 (00620204)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 細胞骨格 / アクチン / フォルミン / コフィリン / 螺旋回転 / 螺旋構造

Research Abstract

In cells, the formation of actin structures is regulated by the interaction between actin regulatory proteins. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables. A mammalian formin mDia1 rotates along the long-pitch helix of F-actin during processive actin elongation (helical rotation). Helical rotation may impose torsional force on F-actin in the opposite direction to the twisting of F-actin by an actin depolymerizing factor cofilin. In the present study, we revealed that helical rotation of mDia1 imposes torsional force on F-actin and enhances resistant against the cofilin binding and the filament severing activity of cofilin. In addition, an active mutant of mDia1 tethered to cellular structures through its N-terminal region induces the formation of F-actin resistant to actin disassembly. These results indicate that helical rotation of mDia1 functions as an antagonistic mechanism to the cofilin activity.

Research Products

• [Journal Article] Rotational movement of formins evaluated by using single-molecule fluorescence polarization (2014)
  • Author(s): Mizuno, H. and Watanabe, N.
  • Journal Title: Methods Enzymol Volume: 540 Pages: 73-94
  • DOI: 10.1016/B978-0-12-397924-7.00005-4
  • Peer Reviewed
• [Journal Article] New single-molecule speckle microscopy reveals modification of the retrograde actin flow by focal adhesions at nanometer scales (2014)
  • Author(s): Yamashiro, S., Mizuno, H., Smith, M. B., Ryan, G. L., Kiuchi, T., Vavylonis, D. and Watanabe, N.
  • Journal Title: Mol. Biol. Cell Volume: 25 Pages: 1010-1024
  • DOI: 10.1091/mbc.E13-03-0162
  • Peer Reviewed
• [Journal Article] F- and G-actin homeostasis regulates mechanosensitive actin nucleation by formins (2013)
  • Author(s): Higashida, C., Kiuchi, T., Akiba, Y., Mizuno, H., Maruoka, M., Narumiya, S., Mizuno, K. and Watanabe, N.
  • Journal Title: Nat. Cell Biol Volume: 15 Pages: 395-405
  • DOI: 10.1038/ncb2693
  • Peer Reviewed
• [Journal Article] mDial and formins : screw cap of the actin filament (2012)
  • Author(s): Mizuno, H. and Watanabe, N.
  • Journal Title: Biophysics Volume: 8 Pages: 95-102
  • DOI: 10.2142/biophysics.8.95
  • Peer Reviewed
• [Journal Article] フォルミンタンパク質のアクチン二重螺旋に沿った回転重合 (2012)
  • Author(s): 渡邊直樹,水野裕昭
  • Journal Title: 化学と生物 Volume: 第50巻第11号 Pages: 801‐806
  • URL: https://www.jstage.jst.go.jp/article/kagakutoseibutsu/50/11/50_801/_pdf
  • Peer Reviewed
• [Journal Article] アクチン研究の最新動向―構造から調節,恒常性,可視化,モデリングまで (2012)
  • Author(s): 山城佐和子、圓岡真宏、水野裕昭、渡邊直樹
  • Journal Title: 実験医学 Volume: 第30巻第18号 Pages: 2998-3005
  • Peer Reviewed
• [Presentation] 一分子蛍光偏光を用いたアクチン線維の螺旋構造に沿ったフォルミンの回転運動の可視化 (2013)
  • Author(s): 水野裕昭、山城佐和子、渡邊直樹
  • Organizer: 日本顕微鏡学会第57回シンポジウム
  • Place of Presentation: 名古屋 (口頭)
  • Year and Date: 2013-11-16
  • Invited
• [Presentation] Actin filament stabilization by helical rotation of mammalian formin mDial (2012)
  • Author(s): 水野裕昭、山城佐和子、渡邊直樹
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡 (口頭)
  • Year and Date: 2012-12-12