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Rab13 is a downstream effector of Mst1 to mediate LFA-1 activation critical for lymphocyte trafficking.

Research Project

Project/Area Number 24590588
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionKitasato University

Principal Investigator

KATAGIRI Koko  北里大学, 理学部, 教授 (00322157)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsLFA-1 / migration / Rap1 / Mst1 / Rab13 / cell polarization / leading edge / 接着カスケード / インテグリン / 遊走 / 細胞極性 / ケモカイン / 動態 / シグナル伝達 / 免疫動態
Outline of Final Research Achievements

In this study, we report an essential link between Rab13 and Mst1 in lymphocyte adhesion and migration. Mst1 promoted the phosphorylation of DENND1C to activate Rab13 with chemokine. Active Rab13 associated with Mst1, and facilitated to deliver LFA-1 to the leading edge of lymphocytes by recruitment of myosin Va along actin cables, which extended through the localization of VASP to the cell periphery via MST1-dependent phosphorylation at Ser-157. The inhibition of Rab13 function reduced adhesion and migration on ICAM-1, and LFA-1 ring formation of T cells at contact zone with antigen-presenting cells. Rab13-deficient mice had hypoplastic lymphoid tissues due to the defective trafficking capability of lymphocytes. These results indicate that Rab13 acts with Mst1 to regulate the spatial distribution of LFA-1, and the motility and interaction dynamics of lymphocytes.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2014 2013 2012

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

  • [Journal Article] Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking.2014

    • Author(s)
      Nishikimi A, Ishihara S, Ozawa M, Etoh K, Fukuda M, Kinashi T and Katagiri K
    • Journal Title

      Sci. Signal.

      Volume: Vol. 7, Issue 336 Issue: 336

    • DOI

      10.1126/scisignal.2005199

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] HTLV-1 bZIP Factor Induces Inflammation through Labile Foxp3 Expression.2013

    • Author(s)
      Yamamoto-Taguchi N, Satou Y, Miyazato P, Ohshima K, Nakagawa M, Katagiri K, Kinashi T, Matsuoka M.
    • Journal Title

      PLoS Pathog.

      Volume: 9(9):e1003630. Issue: 9 Pages: 1-12

    • DOI

      10.1371/journal.ppat.1003630

    • NAID

      120005341884

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Rab13 is a downstream effector of Mst1 to mediate LFA-1 activation crucial for lymphocyte trafficking.2014

    • Author(s)
      Nishikimi A, Ishihara S, Ozawa M, Kinashi T, Katagiri K.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都府、京都市、国立京都国際会館
    • Year and Date
      2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular mechanisms of Rab13-depedent transport of LFA-1 during lymphocyte chemotaxis.2014

    • Author(s)
      Tanno S, Nishikimi A, Ishihara S, Katagiri K.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都府、京都市、国立京都国際会館
    • Year and Date
      2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] ケモカインに応答したリンパ球の遊走におけるRab13を介したLFA-1輸送機構の解明2014

    • Author(s)
      石塚大地、錦見昭彦、石原沙耶花、片桐晃子
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県、横浜市、パシフィコ横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Rab13はMst1の下流分子であり、LFA-1の局在制御を介してリンパ球の遊走を制御している2014

    • Author(s)
      大内裕太朗、錦見昭彦、石原沙耶花、小沢まどか、福田光則、木梨達雄、片桐晃子
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県、横浜市、パシフィコ横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 生殖器の上皮および腺組織の細胞増殖におけるRab13の役割2014

    • Author(s)
      勝又美菜子、錦見昭彦、石原沙耶花、三枝信、片桐晃子
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県、横浜市、パシフィコ横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Lymphocyte arrest was induced by the binding of active Rap1 to filamins.2012

    • Author(s)
      Sayaka Ishihara, Tatsuo Kinashi, Koko Katagiri
    • Organizer
      日本免疫学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulation of LFA-1/ICAM-1-dependent adhesion and migration by Rab13.2012

    • Author(s)
      Suda Hidetsugu, Mitsunari Fikuda, Tatsuo Kinashi, Koko Katagiri
    • Organizer
      日本免疫学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Critical roles of Spa-1 in chemokine-induced Rap1 activation.2012

    • Author(s)
      Shimizu Haruka, Sayaka Ishihara, Joe Inoue, Nagaharu Minato,Tatsuo Kinashi, Koko Katagiri
    • Organizer
      日本免疫学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report

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

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