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樹状細胞の3次元での動きを制御する分子ネットワークとその時空間ダイナミクス

Publicly Offered Research

Project AreaCross-talk between moving cells and microenvironment as a basis of emerging order in multicellular systems
Project/Area Number 23111522
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 InstitutionKyushu University

Principal Investigator

福井 宣規  九州大学, 生命防御医学研究所, 教授 (60243961)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2011: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords細胞運動 / 遺伝子改変マウス / シグナル伝達 / 低分子量Gタンパク質
Research Abstract

細胞運動は、膜の極性化と細胞骨格のダイナミクスを必要とする最も基本的な細胞機能の1つであり、2次元での解析結果から、RacやRho、脂質キナーゼやホスファターゼといったシグナル分子の時空間制御の重要性が指摘されてきた。しかしながら近年、3次元での細胞運動に特異的に必要とされるシグナル分子が同定されるに至り、新たなパラダイムの構築が急務となっている。本研究は、DOCK8を欠損した樹状細胞では、3次元環境下での遊走が特異的に障害されるという申請者の知見を基に、その制御機構を解明することを目的とする。このため本年度は、以下のような研究を行い、研究の進展につながる成果を得た。
1.T細胞や好中球を用いて遊走実験を行い、これらの細胞においても、DOCK8欠損により3次元環境下での遊走が障害されることを確認した。
2.レトロウイルスベクターを用いて、Lifeact-GFPやミオシンL鎖-GFPを、DOCK8欠損細胞に発現させることに成功した。
3.プルダウン法で解析する限り、DOCK8欠損樹状細胞でも、Cdc42の活性化は正常におこることを見いだした。これは恐らく、他のGEFにより、DOCK8欠損の影響が機能的に代償されているためだと考えられ、空間情報を加味した研究の必要性が示唆された。
4.DOCK8の発現を欠く細胞株に、HAタグを融合させた野生型DOCK8およびその欠失変異体を発現させたトランスフェクタントを樹立し、DOCK8の局在や機能に重要なドメインを同定した。

Report

(2 results)
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (23 results)

All 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (14 results) Remarks (2 results)

  • [Journal Article] Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration2012

    • Author(s)
      Terasawa M, Uruno T, Mori S, Kukimoto-Niino M, Nishikimi A, Sanematsu F, Tanaka Y, Yokoyama S, Fukui Y
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 9 Pages: e46277-e46277

    • DOI

      10.1371/journal.pone.0046277

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migrataon during immune responses2012

    • Author(s)
      Yosuke Harada, Yoshihiko Tanaka, Masao Terasawa, Markus Pieczyk, Katsuyoshi Habiro, Tomoya Katakai, Kyoko Hanawa-Suetsugu, Mutsuko Kukimoto-Niino, Tomoko Nishizaki, Mikako Shirouzu, Xuefeng Duan, Takehito Uruno, Akihiko Nishikimi, Fumiyuki Sanematsu, Shigeyuki Yokoyama, Jens V.Stein, Tatsuo Kinashi, Yoshinori Fukui
    • Journal Title

      Blood

      Volume: (In press) Issue: 19 Pages: 4451-4461

    • DOI

      10.1182/blood-2012-01-407098

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activatorDOCK22012

    • Author(s)
      Nishikimi A, Uruno T, Duan X, Cao Q, Okamura Y, Saitoh T, Saitoh N, Sakaoka S, Du Y, Suenaga A, Kukimoto-Niino M, Miyano K, Gotoh K, Okabe T, Sanematsu F, Tanaka Y, Sumimoto H., Honma T, Yokoyama S, Nagano T, Kohda D, Kanai M, and Fukui Y
    • Journal Title

      Chem. Biol

      Volume: 19 Issue: 4 Pages: 488-497

    • DOI

      10.1016/j.chembiol.2012.03.008

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses2012

    • Author(s)
      Harada Y, et al
    • Journal Title

      Blood

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK22012

    • Author(s)
      Nishikimi A, et al
    • Journal Title

      Chem.Biol.

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for mutual relief of the Rac guanine nucleotide exchange factor DOCK2 and its partner ELMO1 from their autoinhibited forms2012

    • Author(s)
      Hanawa-Suetsugu K, et al
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: 109 Pages: 3305-3310

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization2011

    • Author(s)
      Ippagunta SK, et al
    • Journal Title

      Nature Immunol.

      Volume: 12 Issue: 10 Pages: 1010-1018

    • DOI

      10.1038/ni.2095

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 免疫系細胞高次機能を司るCDMファミリー分子DOCK2-その分子基盤と創薬への応用-2012

    • Author(s)
      福井宣規
    • Organizer
      平成23年度ターゲットタンパク研究プログラム公開シンポジウム
    • Place of Presentation
      学術総合センター(東京)(招待講演)
    • Year and Date
      2012-03-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒト免疫不全症の責任分子DOCK8の生理的機能とその制御2012

    • Author(s)
      田中芳彦, 他
    • Organizer
      第22回 Kyoto T Cell Conference
    • Place of Presentation
      和順会館(京都府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of a signaling molecule critical for dendritic cell migration in three-dimensional environments2012

    • Author(s)
      Harada Y, et al
    • Organizer
      The 21st Hot Spring Harbor Symposium jointly with 9th Global COE International Symposium and 8th Young Investigators Forum
    • Place of Presentation
      九州大学(福岡)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulation of NK cell-mediated cytotoxicity by the atypical Rac activators2011

    • Author(s)
      Sakai Y, et al
    • Organizer
      The 10th Global COE International Symposium and 7th Young Investigation Forum
    • Place of Presentation
      National University of Singapore (Singapore)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Functional significance of DOCK2 dimerization in lymphocyte Migration2011

    • Author(s)
      Yanagihara T, et al
    • Organizer
      The 10th Global COE International Symposium and 7th Young Investigation Forum
    • Place of Presentation
      National University of Singapore (Singapore)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of a signaling molecule critical for dendritic cell migration in three-dimensional environments2011

    • Author(s)
      Harada Y, et al
    • Organizer
      The 10th Global COE International Symposium and 7th Young Investigation Forum
    • Place of Presentation
      National University of Singapore (Singapore)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulation of FcεRI-mediated mast cell degranulation by the atypical GEF2011

    • Author(s)
      Ogawa K, et al
    • Organizer
      The 10th Global COE International Symposium and 7th Young Investigation Forum
    • Place of Presentation
      National University of Singapore (Singapore)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Structural basis of functional complex formation between DOCK2 and ELMO12011

    • Author(s)
      Watanabe M, et al
    • Organizer
      The 10th Global COE International Symposium and 7th Young Investigation Forum
    • Place of Presentation
      National University of Singapore (Singapore)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 樹状細胞の遊走・活性化におけるDOCKファミリー分子の役割とその制御2011

    • Author(s)
      福井宣規
    • Organizer
      第32回和漢医薬学総合研究所特別セミナー「和漢薬治療のターゲットとしての粘膜免疫機構」
    • Place of Presentation
      富山大学(富山)(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] リンパ球遊走におけるDOCK2ダイマー形成の機能的意義2011

    • Author(s)
      寺澤公男, 他
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 免疫特異的なRac活性化因子DOCK2を標的とした免疫抑制剤の開発2011

    • Author(s)
      錦見昭彦, 他
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Role of phospholipid in DOCK family protein-mediated cellular functions2011

    • Author(s)
      Fukui Y, et al
    • Organizer
      第10回日本生化学会JBSバイオフロンティアシンポジウム
    • Place of Presentation
      Hotel Luigans(福岡)(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] リンパ球遊走におけるDOCK2ダイマー形成の機能的意義2011

    • Author(s)
      寺澤公男, 他
    • Organizer
      第21回Kyoto T Cell Conference
    • Place of Presentation
      京都平安ホテル(京都)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Control of cardiovascular development by the atypical Rac activator DOCK1802011

    • Author(s)
      Sanenatsu F, et al
    • Organizer
      The 6th International symposium of Institute Network
    • Place of Presentation
      東京医科歯科大学(東京)
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/iden/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/iden/

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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