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New mechanisms of perinatal cardiovascular regulation by class II PI3K

Research Project

Project/Area Number 18K15010
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48020:Physiology-related
Research InstitutionKanazawa University

Principal Investigator

Aki Sho  金沢大学, 医学系, 助教 (80767210)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsホスホイノシタイド / PI3キナーゼ / エンドサイトーシス / 循環調節 / 平滑筋収縮 / PI3K / ミトコンドリア / メンブレントラフィッキング / PI3K-C2α / PI3K-C2β / 周生期循環適応
Outline of Final Research Achievements

Class II phosphoinositide3-kinases (PI3Ks), PI3K-C2α andPI3K-C2β, are highly homologous and distinct from class I and class III PI3Ks in catalytic products and domain structures. In contrast to class I and class III PI3Ks, physiological roles of class II PI3Ks are not fully understood. We studied the phenotypes of cardiomyocyte or smooth muscle–specific knockout (KO) mice of PI3K-C2α and PI3K-C2β. Cardiomyocyte specific PI3K-C2α and PI3K-C2β double KO(DKO) mice show heart failure due to collapse of the sarcomere structure and abnormally mitochondrial accumulation. In smooth muscle–specific KO mice show that the pup numbers from single PI3K- C2α–KO and single PI3K-C2β–KO mothers were similar to those of control, but those from double KO(DKO)mothers were smaller compared with control.

Academic Significance and Societal Importance of the Research Achievements

PI3Kは3つのクラスが存在し、I型PI3KはPI(3,4,5)P3を産生して細胞遊走や細胞増殖に関与し、III型PI3KはPI(3)Pを産生してオートファジーを制御する。一方II型PI3Kの機能は、申請者のグループがPI3K-C2α KOマウスを報告するまで不明であった。内皮細胞においてPI3K-C2αは主としてPI(3,4)P2を産生し、受容体エンドサイトーシスに必須である。II型PI3Kは、I型・III型PI3Kとは異なる、独自の生命維持機能を担っている。II型PI3K機能の類似の研究はなく、周生期適応におけるII型PI3K機能の解明により、PIによる膜動現象制御の理解が進展する。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] TGFβ receptor endocytosis and Smad signaling require synaptojanin1?, PI3K-C2α?, and INPP4B?mediated phosphoinositide conversions2020

    • Author(s)
      Aki Sho、Yoshioka Kazuaki、Takuwa Noriko、Takuwa Yoh
    • Journal Title

      Molecular Biology of the Cell

      Volume: 31(5) Issue: 5 Pages: 360-372

    • DOI

      10.1091/mbc.e19-11-0662

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Class II phosphatidylinositol 3-kinase α and β isoforms are required for vascular smooth muscle Rho activation, contraction and blood pressure regulation in mice2020

    • Author(s)
      Islam Shahidul、Yoshioka Kazuaki、Aki Sho、Ishimaru Kazuhiro、Yamada Hiroki、Takuwa Noriko、Takuwa Yoh
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 70 Issue: 1 Pages: 18-18

    • DOI

      10.1186/s12576-020-00745-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The class II phosphoinositide 3-kinases PI3K-C2α and PI3K-C2β differentially regulate clathrin-dependent pinocytosis in human vascular endothelial cells.2019

    • Author(s)
      Aung KT, Yoshioka K, Ishimaru K, Aki S, Takuwa N, and Takuwa Y.
    • Journal Title

      Journal of Physiological Sciences

      Volume: 69 Issue: 2 Pages: 263-280

    • DOI

      10.1007/s12576-018-0644-2

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Class II PI3Ks α nad β are required for Rho-dependent uterine smooth muscle contraction and parturition in mice.2019

    • Author(s)
      Sarker AK, Aki S, Yoshioka K, Kuno K, Okamoto Y, Ishimaru K, Takuwa N, and Takuwa Y.
    • Journal Title

      Endocrinology

      Volume: 160 Issue: 1 Pages: 235-248

    • DOI

      10.1210/en.2018-00756

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages.2018

    • Author(s)
      Zhao J, Okamoto Y, Asano Y, Ishimaru K, Aki S, Yoshioka K, Takuwa N, Wada T, Inagaki Y, Takahashi C, Nishiuchi T, Takuwa Y.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 5 Pages: e0197604-e0197604

    • DOI

      10.1371/journal.pone.0197604

    • NAID

      120006605152

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MTMR4, a phosphoinositide specific 3’-phosphatase, regulates TFEB activity and the endocytic and autophagic pathways.2018

    • Author(s)
      Pham HQ, Yoshioka K, Mohri H, Nakata H, Aki S, Ishimaru K, Takuwa N, and Takuwa Y.
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 8 Pages: 670-687

    • DOI

      10.1111/gtc.12609

    • NAID

      120006621947

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Sequential phosphoinositide conversion is required for TGFβ-induced receptor endocytosis and endosomal receptor signaling in endothelial cells2020

    • Author(s)
      Sho Aki, Kazuaki Yoshioka, Noriko Takuwa, Yoh Takuwa
    • Organizer
      第97回 日本生理学会大会(大分・別府)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Differential roles of class II PI3-kinase-C2α and -C2β in clathrinmediated fluid phase endocytosis in vascular endothelial cells2020

    • Author(s)
      Kazuaki Yoshioka, Sho Aki, Noriko Takuwa, Yoh Takuwa
    • Organizer
      第97回 日本生理学会大会(大分・別府)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sequential phosphoinositide conversion is required for transforming growth factor β-induced receptor endocytosis and Smad2/3 activation in endothelial cells2019

    • Author(s)
      Sho Aki, Kazuaki Yoshioka, Noriko Takuwa, Yoh Takuwa
    • Organizer
      60th International Conference on the Bioscience of Lipids, Hitotsubashi Hall (Tokyo)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Differential roles of class II PI3K in endocytosis and endosomal signaling2019

    • Author(s)
      Kazuaki Yoshioka, Khin Thuzar Aung, Md Azadul Kabir Sarker, Sho Aki, Kuntal Biswas, Noriko Takuwa, Yoh Takuwa
    • Organizer
      60th International Conference on the Bioscience of Lipids, Hitotsubashi Hall (Tokyo)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 連続するホスホイノシタイド代謝がTGFβ受容体エンドサイトーシス及びSmad2/3 活性化に必須である2019

    • Author(s)
      安藝 翔、吉岡和晃、多久和典子、多久和 陽
    • Organizer
      第61回 日本脂質生化学会、北海道大学(札幌)
    • Related Report
      2019 Annual Research Report
  • [Presentation] イノシトールリン脂質3’脱リン酸化酵素MTMR4 による細胞内クリアランス制御メカニズム2019

    • Author(s)
      吉岡和晃、Quynh Hoa Pham、安藝 翔、多久和典子、多久和 陽
    • Organizer
      第61回 日本脂質生化学会、北海道大学(札幌)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質リン酸化酵素クラスII型PI3キナーゼ による循環機能制御の新機構2019

    • Author(s)
      安藝 翔
    • Organizer
      先端モデル動物支援プラットフォーム若手支援技術講習会(蓼科)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 連続するホスホイノシタイド代謝がTGFβ受容体エンドサイトーシス及びSmad2/3活性化に必須である2019

    • Author(s)
      安藝 翔、吉岡和晃、Islam Shahidul、多久和典子、多久和 陽
    • Organizer
      第92回日本生化学会大会、横浜パシフィコ(横浜)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞膜イノシトールリン脂質脱リン酸化酵素・MTMR4による細胞内クリアランスの制御2019

    • Author(s)
      吉岡和晃、Quynh Hoa Pham、安藝 翔、多久和典子、多久和 陽
    • Organizer
      第92回日本生化学会大会、横浜パシフィコ(横浜)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sequential phosphoinositide conversion is required for transforming growth factor -induced receptor endocytosis and Smad2/3 activation in endothelial cells2019

    • Author(s)
      Sho Aki
    • Organizer
      FAOPS2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脂質リン酸化酵素II型PI3キナーゼ による循環機能制御の新機構2019

    • Author(s)
      安藝 翔
    • Organizer
      第5回血管生物若手研究会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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