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Spatio-temporal analysis of DOCK180 during dorsal ruffle formation

Research Project

Project/Area Number 24770127
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionKyushu University

Principal Investigator

SANEMATSU FUMIYUKI  九州大学, 生体防御医学研究所, 助教 (80381094)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsラッフル膜形成 / Rac活性化分子 / DOCK180 / 細胞骨格 / Rac / ホスファチジン酸 / ラッフル膜
Research Abstract

Activation of receptor tyrosine kinases leads to the formation of two different types of plasma membrane structures: peripheral ruffles and dorsal ruffles. Although the formation of both ruffle types requires activation of the small GTPase Rac, the difference in kinetics suggests that a distinct regulatory mechanism operates for their ruffle formation. DOCK1(DOCK180) and DOCK5 are atypical Rac activators and are both expressed in mouse embryonic fibroblasts (MEFs). We found that DOCK1 deficiency alone impaired dorsal ruffle formation in MEFs. DOCK1 bound to phosphatidic acid (PA) through the C-terminal polybasic amino acid cluster and was localized to dorsal ruffles. In addition, we show that phospholipase D, an enzyme that catalyzes PA synthesis, is required for PDGF-induced dorsal, but not peripheral, ruffle formation. These results indicate that the phospholipase D-PA axis selectively controls dorsal ruffle formation by regulating DOCK1 localization.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (14 results)

All 2013 2012 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation2013

    • Author(s)
      Sakai, Y., Tanaka, Y., Yanagihara, T., Watanabe, M., Duan, X., Terasawa, M., Nishikimi, A., Sanematsu, F., Fukui. Y.
    • Journal Title

      Blood

      Volume: 122(3) Pages: 386-93

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphatidic acid-dependent recruitment and function of the Rac activator DOCK1 during dorsal ruffle formation2013

    • Author(s)
      Sanematsu, F., Nishikimi, A., Watanabe, M., Hongu, T., Tanaka, Y., Kanaho, Y., Côté, J.F., Fukui, Y.
    • Journal Title

      J Biol. Chem.

      Volume: 288(12) Pages: 8092-100

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation2013

    • Author(s)
      Sakai Y, Tanaka Y, Yanagihara T, Watanabe M, Duan X, Terasawa M, Nishikimi A, Sanematsu F, Fukui Y.
    • Journal Title

      Blood

      Volume: 122 Issue: 3 Pages: 386-393

    • DOI

      10.1182/blood-2012-12-475897

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphatidic acid-dependent recruitment and function of the Rac activator DOCK1 during dorsal ruffle formation.2013

    • Author(s)
      Sanematsu F, Nishikimi A, Watanabe M, Hongu T, Tanaka Y, Kanaho Y, Cote JF, Fukui Y
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 12 Pages: 8092-8100

    • DOI

      10.1074/jbc.m112.410423

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 心血管形成におけるDOCK180の機能とその制御機構2013

    • Author(s)
      實松史幸
    • Journal Title

      感染 炎症 免疫

      Volume: 42 Pages: 50-53

    • Related Report
      2012 Research-status Report
  • [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(9)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK22012

    • Author(s)
      Nishikimi, A., Uruno, T., Duan, X., Cao, Q., Okamura, Y., Saitoh, T., Saito, 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., Fukui, Y.
    • Journal Title

      Chem. Biol.

      Volume: 19(4) Pages: 488-97

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses2012

    • Author(s)
      Harada, Y., Tanaka, Y., Terasawa, M., Pieczyk, M., Habiro, K., Katakai, T., Hanawa-Suetsugu, K., Kukimoto-Niino, M., Nishizaki, T., Shirouzu, M, Duan, X., Uruno, T., Nishikimi, A., Sanematsu, F., Yokoyama, S., Stein, J.V., Kinashi, T., Fukui, Y.
    • Journal Title

      Blood

      Volume: 119(19) Pages: 4451-61

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [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 Research-status 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 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Presentation] Dorsal ruffle形成時におけるDOCK1の役割とその制御2012

    • Author(s)
      實松史幸, 錦見昭彦, 渡邉真裕紀, 本宮綱記, 田中芳彦, 金保安則, Jean-Francois Cote, 福井宣規
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of DOCK1 and Its Regulation during Dorsal ruffle formation.

    • Author(s)
      Sanematsu F et al.
    • Organizer
      The 35th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      Marinemesse Fukuoka, Japan
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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