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構造情報を活用した細胞質分裂の分子メカニズムの解明

Publicly Offered Research

Project AreaStructural basis of cell-signalling complexes mediating signal perception, transduction and responses
Project/Area Number 25121714
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOita University

Principal Investigator

石崎 敏理  大分大学, 医学部, 教授 (70293876)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsRho / アクチン細胞骨格 / mDia / 細胞質分裂 / 生体機能 / Anillin / CitronK
Outline of Annual Research Achievements

mDiaはフォルミン相同蛋白質に属し、哺乳類細胞では3つのアイソフォームmDia1,2,3が発現しており、直鎖状のアクチン線維の形成を担う。3つのアイソフォームの中でもmDia2細胞質分裂に強く関与している。mDia2の細胞質分裂への関与は収縮環近傍でのanillinとの結合することで細胞収縮装置を収縮環に安定的に局在させ、細胞分裂の完遂に寄与する。本研究ではその機構の原子レベルの解析を目的にmDia2-anillin複合体の結晶構造解析を行った。mDia2の異なる長さの部分断片を調整し結晶化を試み、微小結晶を得られた。しかしながら結晶解析を行うに十分な回折像は得られていない。問題点として、mDia2部分断片は単独でも結晶化できないことから、mDia2のanillin領域の結晶化させるためには、その構造を安定化させる何らかのsubstrate(本研究ではanillin断片)との共結晶を得ることが不可欠であると考えられる。mDiaは分子内に複数のdimer形成領域を有しているが、用いているmDia2部分断片 はそのうち1つのdimer領域を含んでいる。精製したmDia2-anillin複合体のstoichiometryは2:1になっていること、また前述したmDia2単独での結晶化ができないことを併せて考えると、結晶を得るためにはmDia2-anillin複合体のstoichiometryを2:2にする必要があると考えられる。そこで、現在過剰量のanillin断片用いて結晶化結晶化を行っている。あわせて、mDia2-anillin複合体を安定化させる第3のタンパク質の同定し、本タンパク質の細胞分裂への関与と機序の解析を行っている。
それ以外に、mDia1のがん化に果たす役割、ROCKの生体機能についてもあわせて解析を行っている。

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。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (11 results)

All 2015 2014 2013

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Protective effect of hydrogen sulfide on pancreatic beta-cells.2015

    • Author(s)
      Okamoto M, Ishizaki T, Kimura T
    • Journal Title

      Nitric Oxide

      Volume: 46 Pages: 32-36

    • DOI

      10.1016/j.niox.2014.11.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interplay between Rab27a effectors in pancreatic beta-cells.2015

    • Author(s)
      Yamaoka M, Ishizaki T, Kimura T
    • Journal Title

      World Journal of Diabetes

      Volume: 6 Pages: 508-516

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GTP- and GDP-dependent Rab27a effectors in pancreatic beta-cells2015

    • Author(s)
      Yamaoka M, Ishizaki T, Kimura T
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 38 Pages: 1-6

    • NAID

      130005068105

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis.2013

    • Author(s)
      Watanabe S, De Zan T, Ishizalki T, Yasuda S, Kamijo H, Yamada D, Aoki T, Kiyonari H, Kaneko H, Shimizu R, Yamamoto M, Goshima G, and, Narummiya S
    • Journal Title

      Cell Reports

      Volume: 5(4) Issue: 4 Pages: 926-932

    • DOI

      10.1016/j.celrep.2013.10.021

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EphA4-dependent axon retraction and midline localization of Ephrin-B3 are disrupted in the spinal cord of mice lacking mDial and mDia3 in combination2013

    • Author(s)
      Yosuke Toyoda, Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Hiroshi Nishimaru, Hiroyuki Hioki, Takeshi Kaneko, Toshimasa Ishizaki, Tomoyuki Fnruyashiki and Shuh Narumiva
    • Journal Title

      Genes to Cells

      Volume: 18 Issue: 10 Pages: 873-885

    • DOI

      10.1111/gtc.12081

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Citron-kinase mediates trasition from constriction to abscission through its coiled-coil domain2013

    • Author(s)
      Watanabe S, De Zan T, Ishizaki T, Narumiya S.
    • Journal Title

      Journal of Cell Science

      Volume: (印刷中(in press) Pages: 1773-1784

    • DOI

      10.1242/jcs.116608

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes Biochem2013

    • Author(s)
      Okamoto M, Yamaoka M, Takei M, Ando T, Taniguchi S, Ishii I, Tohya K, Ishizaki T, Niki I, Kimura T
    • Journal Title

      Biophys. Res. Commun

      Volume: 442 Issue: 3-4 Pages: 227-233

    • DOI

      10.1016/j.bbrc.2013.11.023

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated Cdc42-bound-IQGAP1 determines the cellular endocytic site2013

    • Author(s)
      Kimura T, Yamaoka M, Taniguchi S, Okamoto M, Takei M, Ando T, Iwamatsu A, Watanabe T, Kaibuchi K, Ishizaki T, Niki I
    • Journal Title

      Mol. Cell. Biol

      Volume: 33 Issue: 24 Pages: 4834-43

    • DOI

      10.1128/mcb.00895-13

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of Rab27a-GAP-interacting proteins and its functional analysis in pancreatic beta-cells.2014

    • Author(s)
      Yamaoka M, Ando T, Okamoto M, Terabayashi T, Matsunaga K, Ishizaki R, Izumi T, Niki I, Ishizaki T, Kimura T
    • Organizer
      50th Annual meeting of European Association for the Study of Diabetes
    • Place of Presentation
      Reed Messe Vienna, Vienna, Austria
    • Year and Date
      2014-09-15 – 2014-09-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes.2014

    • Author(s)
      •Okamoto M, Yamaoka M, Ando T, Takei M, Taniguchi S, Terabayashi T, Niki I,Ishizaki T, Kimura T
    • Organizer
      3rd International Conference on Hydrogen Sulfide in Biology and Medicine
    • Place of Presentation
      Kyoto university, Kyoto, Japan
    • Year and Date
      2014-06-04 – 2014-06-06
    • Related Report
      2014 Annual Research Report
  • [Book] Ras Superfamily Small G Proteins: Biology and Mechanisms2014

    • Author(s)
      Ishizaki T and Narumiya S
    • Total Pages
      33
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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