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Deciphering the function for S1P transporter, Spns2, in mammals

Research Project

Project/Area Number 24370084
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cell biology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

MOCHIZUKI Naoki  独立行政法人国立循環器病研究センター, 研究所, 部長 (30311426)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Hiroyuki  国立循環器病研究センター, 研究所, 研究員 (10467657)
Co-Investigator(Renkei-kenkyūsha) FUKUHARA Shigetomo  国立循環器病研究センター, 研究所, 室長 (70332880)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywordsスフィンゴシン1燐酸 / ノックアウトマウス / 輸送体 / リンパ球 / 胸腺 / 骨髄 / S1P / 眼瞼 / 蛋白質 / 遺伝子 / 動物 / トランスポーター / スフィンゴ脂質
Outline of Final Research Achievements

We had identified Spns2 as a S1P transporter in zebrafish. Therefore, we aimed at studying the function of Spns2 in mammals in S1P signaling.
First, we developed global Spns2 knockout (KO) mice and analyzed the number of lymphocytes in primary and secondary lymphatic organs, because S1P is known to be essential for egress from the primary lymphatic organs. Mature T- and B- lymphocytes in the blood were decreased. Mature T-lymphocytes were accumulated in the thymus. Consistently, the number of mature T-lymphocytes was decreased in the secondary lymphatic organs. Similarly, the number of mature B-lymphocytes in the bone marrow and the secondary lymphatic organs was decreased, suggesting that the egress of T- and B-lymphocytes were decreased. The endothelium-specific Spns2 KO mice exhibited the similar phenotype found in global KO mice. These data indicate that endothelial Spns2 functions as a S1P transporter to induce the egress of lymphocytes from the primary lumphatic organs.

Report

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

    (12 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (5 results) (of which Invited: 2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] S1P-Yap1 signaling regulates endoderm formation required for cardiac precursor cell migration in zebrafish.2014

    • Author(s)
      Fukui H, Terai K, Nakajima H, Chiba A, Fukuhara S, Mochizuki N.
    • Journal Title

      Dev. Cell.

      Volume: 31 Issue: 1 Pages: 128-136

    • DOI

      10.1016/j.devcel.2014.08.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The secreted protein ANGPTL2 promotes metastasis of osteosarcoma cells through integrin alpha5beta1, p38 MAPK, and matrix metalloproteinases.2014

    • Author(s)
      Odagiri et al.
    • Journal Title

      Science Signaling

      Volume: 7 Issue: 309

    • DOI

      10.1126/scisignal.2004612

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rap1 regulates actin cytoskeleton at endothelial cell-cell junctions by spatially controlling myosin II activlty2013

    • Author(s)
      Ando K, S. Fukuhara, Y. Obars, T. Noriya. N. Nakahata, N. Moohizuki.
    • Journal Title

      Journal of Cell Biology

      Volume: 202 Issue: 6 Pages: 901-916

    • DOI

      10.1083/jcb.201301115

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular Endothelial Adrenomedullin-RAMP2 System 18 Essential for Vascular Integrity and Organ Homeostasis2013

    • Author(s)
      Teruhide Koyama. Laura Ochoa-Callejero, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Nobuyoshi Iinuma, Takuma Arai, Takahiro Yoshizawa, Yasuhiro Iesato, Yang Lei, Ryuichi Uetake, Akihiro Yamauchi, Megumu Tanaka, Kyoko Igarashi, Yuichi Tbriyama, Ralf H. Adams, Hayato Kawakami, Naoki Mochizuki, Alfredo Martinez, Takayuki Shindo
    • Journal Title

      Circulation

      Volume: 127 Issue: 7 Pages: 842-853

    • DOI

      10.1161/circulationaha.112.000756

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The sphingosine-I-phosphate transporter Spns2 expressed on endothelial cells regulateslymphocyte trafficking in mice.2012

    • Author(s)
      Fukuhara S, et al
    • Journal Title

      J. Clin. Invest.

      Volume: 122 Pages: 1416-1426

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] S1P-Yap1 signaling regulates endoderm formation required for cardiac precursor cell migration in zebrafish2014

    • Author(s)
      Hajime Fukui, Shigetomo Fukuhara and Naoki Mochizuki
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cdc42 promotes sprouting angiogenesis via Formin-like 3-mediated formation of endothelial cell filopodia in zebrafish2014

    • Author(s)
      Yuki Wakayama, Shigetomo Fukuhara, Koji Ando, Michiyuki Matsuda and Naoki Mochizuki
    • Organizer
      The 18th International Vascular Biology Meeting (IVBM2014)
    • Place of Presentation
      京都 都メッセ
    • Year and Date
      2014-04-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] イメージングによる心臓・血管発生メカニズムの解明2013

    • Author(s)
      望月直樹
    • Organizer
      日本生理学会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] 血管形成ダイナミクスの生体イメージング

    • Author(s)
      福原 茂朋、望月 直樹
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ゼブラフィッシュの蛍光イメージング解析による血管形成メカニズムの解明

    • Author(s)
      福原 茂朋、望月 直樹
    • Organizer
      第21回日本血管生物医学会
    • Place of Presentation
      千里阪急ホテル
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/ncvc

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 心筋細胞増殖誘導剤及びこれを含有する心筋梗塞治療用医薬組成物、並びに心筋細胞の製造方法2013

    • Inventor(s)
      望月直樹
    • Industrial Property Rights Holder
      独立行政法人 国立循環器病研究センター、他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-198591
    • Filing Date
      2013-09-25
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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