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Regulation of membrane trafficking through PI(3)P-metabolizing enzymes in endothelial cells.

Research Project

Project/Area Number 26460292
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionKanazawa University

Principal Investigator

Yoshioka Kazuaki  金沢大学, 医学系, 助教 (80333368)

Research Collaborator BISWAS Kuntal  
AKI Sho  
Kuda Yuichi  
MOHRI Hiromi  
SHIMIZU Shouta  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsPI3キナーゼ / ホスフォイノシチド / 血管内皮細胞 / KOマウス / 血管炎症 / 細胞内小胞輸送 / ノックアウトマウス / 動脈硬化 / 解離性大動脈瘤 / イノシトールリン脂質 / 血管新生 / PI(3)Pホスファターゼ / 粥状動脈硬化 / 血管透過性 / PI(3)P ホスファターゼ
Outline of Final Research Achievements

Phosphatidylinositol 3-kinases (PI3Ks) are the family of lipid kinases responsible for the generation of 3’-phosphoinositides. We have recently reported that class II a-isoform PI3K (C2a) plays a crucial role in developmental and pathological angiogenesis, and is indispensable for the maintenance of the VE-cadherin-mediated EC barrier function and receptor endocytosis. These defects result in impaired vascular homeostasis under the pathophysiological conditions. In this study, we found that among myotubularin-related protein (MTMR) family members, the expression of MTMRx is relatively abundant in ECs. We found that, in HUVECs, MTMRx was localized mainly in the endosomes. Next we analyzed the phenotype of MTMRx global KO mice. MTMRx mice showed normally development but die perinatally. We conclude that C2a regulates vascular homeostasis through controlling PI(3)P+-membrane trafficking, cooperating with MTMRx in ECs.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (18 results)

All 2017 2016 2015 2014 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (1 results)

  • [Journal Article] Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.2017

    • Author(s)
      Serafimidis I, Rodriguez-Aznar E, Lesche M, Yoshioka K, Takuwa Y, Dahl A, Pan D and Gavalas A.
    • Journal Title

      PLOS Biology

      Volume: 15 (3) Issue: 3 Pages: e2000949-e2000949

    • DOI

      10.1371/journal.pbio.2000949

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphatidylinositol 3-kinase Class II α-Isoform PI3K-C2α Is Required for Transforming Growth Factor β-induced Smad Signaling in Endothelial Cells.2015

    • Author(s)
      Aki S, Yoshioka K, Okamoto Y, Takuwa N, Takuwa Y.
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 10 Pages: 6086-6105

    • DOI

      10.1074/jbc.m114.601484

    • NAID

      120005593954

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] クラスII型PI3K-C2α及びPI3K-C2βは血管血管内皮細胞におけるピノサイトーシスに必須である2017

    • Author(s)
      Khin Thuzar Aung, Sho Aki, Kazuaki Yoshioka, Hoa Quynh Pham, Azadul Kabir Sarker, Shahidul Islam, Noriko Takuwa and Yoh Takuwa
    • Organizer
      第94 回日本生理学会大会
    • Place of Presentation
      浜松市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] イノシトールリン脂質特異的3’-ホスファターゼMTMR4はリソソーム機能・オートファジーを制御する2017

    • Author(s)
      Hoa Quynh Pham, Kazuaki Yoshioka, Sato Nakamura, Azadul Kabir Sarker, Khin Thuzar Aung, Shahidul Islam, Sho Aki, Noriko Takuwa and Yoh Takuwa
    • Organizer
      第94 回日本生理学会大会
    • Place of Presentation
      浜松市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Endothelial Class II PI3K-C2α is necessary for vascular formation and integrity through regulating endocytic membrane trafficking2017

    • Author(s)
      吉岡和晃、安藝 翔、多久和典子、多久和 陽
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      金沢市
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞においてクラスII 型PI3K-C2αはTGFβ/Smad シグナル伝達系に必須である2016

    • Author(s)
      安藝 翔、吉岡和晃、岡本安雄、多久和 典子、多久和 陽
    • Organizer
      第93回 日本生理学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Deletion of sphingosine 1-phospahte (S1P) receptor-2 (S1P-2-) inhibits lung fibrosis through altering alveolar macrophage polarization and senescence in mice.2015

    • Author(s)
      Juan juan Zhao Yasuo Okamoto Kazuaki Yoshioka Sho Aki Pham Quynh Hoa Azadul MD Kabir Sarker Khin Thuzar Aung Noriko Takuwa Yutaka Inagaki Chiaki Takahashi Takashi Wada Yoh Takuwa
    • Organizer
      BMB2015(第38回日本分子生物学会・第88回日本生化学会)
    • Place of Presentation
      神戸ポートアイランド(神戸ポートピアホテル 神戸国際会議場 神戸国際展示場 神戸商工会議所)(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] クラス II PI3-キナーゼ PI3K-C2αはエンドソーム上でのTGFβ/Smad2/3シグナリングに必須である2015

    • Author(s)
      安藝 翔、吉岡 和晃、岡本 安雄、多久和 典子、多久和 陽
    • Organizer
      第62回 中部日本生理学会
    • Place of Presentation
      富山大学五福キャンパス 黒田講堂(富山県富山市)
    • Year and Date
      2015-07-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Role of S1P2 in inflammation and fibrosis2015

    • Author(s)
      Yoh Takuwa Juanjuan Zhao, Yasuo, Okamoto, Kazuaki Yoshioka and Noriko Takuwa
    • Organizer
      14 th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
    • Place of Presentation
      Sofitel Chain Bridge Hotel(ハンガリー ブタペスト)
    • Year and Date
      2015-07-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Sphingosine 1-phosphate receptor-2 plays a protective role against anaphylaxis and acute lung injury2015

    • Author(s)
      Yasuo Okamoto, Hong Cui, Kazuaki Yoshioka, Noriko Takuwa, Yoh Takuwa
    • Organizer
      第10回スフィンゴテラピィ(STC)研究会
    • Place of Presentation
      ホテルアローレ(石川県)
    • Year and Date
      2015-06-16
    • Related Report
      2015 Research-status Report
  • [Presentation] クラスII α型PI3K-C2αはエンドソーム上でのTGFβ/Smad2/3 シグナリングに必須である2015

    • Author(s)
      安藝 翔、吉岡和晃、岡本安雄、多久和 典子、多久和 陽
    • Organizer
      第57回 日本脂質生化学会
    • Place of Presentation
      一橋大学一橋講堂(東京)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Sphingosine 1-phosphate receptor-2 plays a protective role against lipopolysaccharide (LPS)-induced acute lung injury2015

    • Author(s)
      Yasuo Okamoto, Hong Cui, Kazuaki Yoshioka, Noriko Takuwa, Sho Aki, JuanJuan Zhao, Hoa Quynh Pham, Md. Azadul Kabir Sarker, Saori Koizumi, Yoh Takuwa
    • Organizer
      第92回 日本生理学会大会
    • Place of Presentation
      神戸国際会議場・展示場(神戸市、兵庫県)
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Research-status Report
  • [Presentation] Novel role of class II PI 3-kinase in in tumor angiogenesis2014

    • Author(s)
      Yoshioka, K.
    • Organizer
      International Symposium on Tumor Microenvironment. –Crosstalk between host and malignant cells
    • Place of Presentation
      金沢大学・自然研図書館・AVホール(Kanazawa, Japan)
    • Year and Date
      2014-11-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] クラスII 型PI3 キナーゼ-C2α によるTGFβ 血管内皮作用の調節機構2014

    • Author(s)
      安藝 翔、吉岡和晃、多久和 典子、岡本安雄、多久和 陽
    • Organizer
      第61回 中部日本生理学会
    • Place of Presentation
      名古屋市立大学桜山キャンパス(愛知県名古屋市)
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] クラスIIα型PI3K-C2αはALK5 内在化及び足場タンパクSARA のエンドソームへの動員を制御しTGF1-Smad2/3 を介した血管新生を調節する2014

    • Author(s)
      安藝 翔、吉岡 和晃、岡本 安雄、多久和 典子、多久和 陽
    • Organizer
      第56回 日本脂質生化学会
    • Place of Presentation
      近畿大学東大阪キャンパス(大阪府東大阪市)
    • Year and Date
      2014-06-06 – 2014-06-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Distinct role of S1P2 in the functional regulation of vascular endothelium and smooth muscle2014

    • Author(s)
      Yoh Takuwa, Yasuo Okamoto, Kazuaki Yoshioka, Noriko Takuwa
    • Organizer
      The 18th International Vascular Biology Meeting 2014 (IVBM 2014)
    • Place of Presentation
      みやこめっせ(京都府京都市)
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Sphingosine-1-phosphate receptor-2 (S1P2) negatively regulates eNOS and protects against acute vascular barrier disruption2014

    • Author(s)
      Yasuo Okamoto, Cui Hong, Kazuaki Yoshioka, Noriko TakuwaToshishige Shibamoto, Yoh Takuwa
    • Organizer
      The 18th International Vascular Biology Meeting 2014 (IVBM 2014)
    • Place of Presentation
      みやこめっせ(京都府京都市)
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Research-status Report
  • [Remarks] 金沢大学 医薬保健研究域医学系 血管分子生理学教室HP

    • URL

      http://physiology1.w3.kanazawa-u.ac.jp

    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2019-12-27  

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