細胞内分子動態の可視化を利用した細胞間情報共有システムの解明

• Project Area: Mutli-dimensional fluorescence live imaging of cellular function and molecular activity
• Project/Area Number: 25113703
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Chiba University
• Principal Investigator: 溝口 貴正 千葉大学, 薬学研究科(研究院), 助教 (10645419)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: 細胞手段移動 / ライブイメージング / 細胞骨格 / ゼブラフィッシュ / 側線原基 / 細胞集団移動

Outline of Annual Research Achievements

動物の器官形成などでみられる細胞の集団移動の強調した移動には移動方向やスピードといった情報の細胞間での共有が必要である。しかしながら情報共有を担う分子メカニズムは未解明な部分も多い。本研究では集団の細胞移動に適したゼブラフィッシュの作戦原基をモデルとして既存の蛍光プローブを利用し解析を行った。前年度までの解析よりE3ユビキチンライゲースであるmib1の変異体で側線原基内の個々の細胞のアクチンのターンオーバーが促進され、アクチンの集積方向が方向性を失い、集団としての移動が破綻することが明らかとなった。本年度は生化学的な解析より、Mib1のターゲットとしてp120ctnを見出した。mib1変異体においてp120ctnを機能阻害すると側線原基の移動が回復することより、細胞集団が情報を共有し協調した移動を行うためにはmib1によるp120ctnの活性制御が不可欠であることが明らかとなった。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Different combinations of Notch ligands and receptors regulate V2 interneuron progenitor proliferation and V2a/V2b cell fate determination (2014)
  • Author(s): Okigawa, S., Mizoguchi, T., Okano, M., Tanaka, H., Isoda, M., Jiang, Y.J., Suster, M., Higashijima, S.-I., Kawakami, K., and Itoh, M.
  • Journal Title: Developmental Biology Volume: 391 Issue: 2 Pages: 196-206
  • DOI: 10.1016/j.ydbio.2014.04.011
  • Peer Reviewed
• [Journal Article] Ricinine: a pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1α (2014)
  • Author(s): Kensuke Ohishi
  • Journal Title: Bioorganic Medicinal Chemistry Volume: 22 Issue: 17 Pages: 4597-4601
  • DOI: 10.1016/j.bmc.2014.07.027
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] The actin dynamics live imaging reveals that Mib1 controls appropriate actin rearrangements and coordinates corrective cell migration. (2015)
  • Author(s): Takamasa Mizoguchi, Kazuya Hirose, Shoko Ikeda, Saori Watanabe, Sasa Yang, Motoyuki Itoh
  • Organizer: Multi-dimensional fluorescence live imaging of cellular function and molecular activities
  • Place of Presentation: Kyoto International Conference Center, Kyoto
  • Year and Date: 2015-01-26 – 2015-01-28
• [Presentation] The appropriate regulation of the Notch signaling activity is required for various neuronal subtypedifferentiation and the neurite outgrowth of V2b interneuron (2014)
  • Author(s): Takamasa Mizoguchi, Mizuki Nakaura, Michi Fukada, Miki Chin, Koichi Kawakami, Motoyuki Itoh.
  • Organizer: Notch研究会
  • Place of Presentation: Osaka Unibversity
  • Year and Date: 2014-12-18
• [Presentation] The appropriate control of the Notch signaling activity is required for various neuronal subtype differentiation and their functions (2014)
  • Author(s): Takamasa Mizoguchi, Mizuki Nakaura, Michi Fukada, Miki Chin, Koichi Kawakami, Motoyuki Itoh.
  • Organizer: 20th Japanese Medaka and Zebrafish Meeting
  • Place of Presentation: Keio University
  • Year and Date: 2014-09-20 – 2014-09-21
• [Presentation] Mib1 regulates cell migration through negative control of Ctnnd1 function by its ubiqutination. (2014)
  • Author(s): Takamasa Mizoguchi, Kazuya Hirose, Shoko Ikeda, Saori Watanabe, Sasa Yang, Motoyuki Itoh.
  • Organizer: 11th International Conference on Zebrafish Development and Genetics
  • Place of Presentation: Madison, Wisconsin,USA
  • Year and Date: 2014-06-24 – 2014-06-28
• [Presentation] Different combinations of Notch ligands and receptors regulate V2 interneuron progenitor proliferation and V2a /V2b cell fate determination. (2014)
  • Author(s): Sayumi Okigawa, Takamasa Mizoguchi, Makoto Okanao, Haruna Tanaka, Miho Isoda, Yun-Jin Jiang, Maximiliano Susuter, Shinichi Higashijima, Koichi Kawakami, Motoyuki Itoh
  • Organizer: 47th Annual Meeting of the Japanese Society of Developmental Biologists
  • Place of Presentation: WINC AICHI, Nagoya, Aichi
  • Year and Date: 2014-05-27 – 2014-05-30
• [Presentation] Mib1 regulates cell migration via ubiqutination of p120ctn (2013)
  • Author(s): 溝口 貴正
  • Organizer: 46th Annual Meeting for Japanese Society of Developmental Biology
  • Place of Presentation: 松江 くにびきメッセ
• [Presentation] Mib1 controls cell migration through negative regulation of p120ctn function by its ubiquitination (2013)
  • Author(s): 溝口 貴正
  • Organizer: The 19th Japanese Medaka and Zebrafish Meeting
  • Place of Presentation: 仙台 仙台市情報・産業プラザ