Conformational plasticity of single molecule regulates actin cytoskeletal rearrangement leading to dynamics in higher structure and function of brain

• Project/Area Number: 26460370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: SAKANE Ayuko 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (60509777)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脳の高次構造・機能 / 小胞輸送 / アクチン細胞骨格の再編成 / Rab13-JRAB系

Outline of Final Research Achievements

We generated a structural model of JRAB/MICAL-L2 through a combination of bioinformatic and biochemical analyses and thereby revealed how JRAB/MICAL-L2 interplays with Rab13 and how its conformational change occurs. Moreover, we elucidated that the conformational plasticity in JRAB/MICAL-L2 causes　spatiotemporal actin cytoskeletal rearrangement to control direction and speed of cell movement and traction force of the cell through a robust approach combining cell biology, live imaging, computational biology, and biomechanics. Thus, our multidisciplinary approach brings a novel concept that the conformational plasticity of a single molecule provides dynamics in higher cellular function. These findings will be of help to understand the dynamics in higher structure and function of brain.

Research Products

• [Journal Article] Conformational Plasticity of JRAB/MICAL-L2 Provides 'Law and Order' (2016)
  • Author(s): A. Sakane, S. Yoshizawa, M. Nishimura, Y. Tsuchiya, N. Matsushita, K. Miyake, K. Horikawa, I. Imoto, C. Mizuguchi, H. Saito, T. Ueno, S. Matsushita, H. Haga, S. Deguchi, K. Mizuguchi, H.
  • Journal Title: Molecular Biology of the Cell Volume: 27 Issue: 20 Pages: 3095-3108
  • DOI: 10.1091/mbc.e16-05-0332
  • Peer Reviewed / Open Access
• [Journal Article] Roles of Rab family small G proteins in formation of the apical junctional complex in epithelial cells (2015)
  • Author(s): Sakane, A. and Sasaki, T.
  • Journal Title: Cell Polarity: Biological Role and Basic Mechanisms Volume: 1 Pages: 349-374
  • DOI: 10.1007/978-3-319-14463-4_15
  • ISBN: 9783319144627, 9783319144634
• [Presentation] Efficient gene-targeting in cultured cells by CRISPR/Cas9 system using non-integrating lentiviral vector（ 非組込型レンチウイルスベクターを用いたCRISPR/Cas9システムによる高効率遺伝子ターゲティング） (2014)
  • Author(s): 松下夏樹、松下佐知、坂根亜由子、佐々木卓也、今村健志
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（ 神奈川県横浜市 ）
  • Year and Date: 2014-11-25
• [Presentation] The conformational plasticity of single molecule provides law and order in collective cell migration（ 集団的細胞運動において１分子の構造変化がつくりだす秩序と法則 ） (2014)
  • Author(s): 坂根亜由子、西村将臣、吉澤信、横田秀夫、佐々木卓也
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（ 京都府京都市 ）
  • Year and Date: 2014-10-17
• [Presentation] The conformational plasticity of JRAB provides law and order in collective cell migration（ 集団的細胞運動においてJRABがつくりだす秩序と法則性 ） (2014)
  • Author(s): 坂根亜由子、西村将臣、横田秀夫、佐々木卓也
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: パシフィコ横浜（ 神奈川県横浜市 ）
  • Year and Date: 2014-09-26
• [Presentation] 集団的細胞運動においてRab13-JRAB系がつくりだす秩序と法則性 (2014)
  • Author(s): 坂根亜由子、西村将臣、吉澤信、横田秀夫、佐々木卓也
  • Organizer: 第66回日本細胞生物学会
  • Place of Presentation: 奈良県新公会堂（ 奈良県奈良市 ）
  • Year and Date: 2014-06-11