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Comprehensive search for novel phospholipids and elucidation of their functions

Research Project

Project/Area Number 22K19287
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Hasegawa Junya  東京医科歯科大学, 難治疾患研究所, 助教 (00533788)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsリン脂質 / 質量分析
Outline of Research at the Start

リン脂質は、細胞膜の主要構成分子として膜の形態変化や構造維持に重要である。リン脂質を特徴付ける極性基の種類は極めて限局的で、コリンやセリン等わずか5種類しか知られていない。申請者は、これまで培ってきたリン脂質の知識・技術と、独自に保有している脂質に特化した最新鋭の質量分析装置を駆使することで、すでに新規リン脂質を4つ同定している。本申請課題は、申請者が考案した独自の手法で、新規極性基を持つリン脂質を包括的に見出し、それらリン脂質群の生理機能解明を目的とする。脂質生物学分野で新しい領域を切り開く挑戦的な研究である。

Outline of Final Research Achievements

Phospholipids have fatty acids at the sn-1 and sn-2 positions of the glycerol backbone, and a characteristic polar group at the sn-3 position. The variety of polar groups in phospholipids is extremely limited, including choline and serine. The reason for this is that lipids are not encoded by genes.
I have already developed a novel method to search for unknown lipids. I have already identified four new phospholipids by my original method. During the period of this study, we attempted to further identify novel phospholipids, but this has not yet been done because I am still in the reviewing stage. In the future, I will accelerate the identification of new lipids as well as the clarification of their functions.

Academic Significance and Societal Importance of the Research Achievements

リン脂質は細胞膜を構成する主要因子であり、細胞・オルガネラの形や固さを制御しているだけでなく、膜を起点とした様々シグナル伝達に寄与している。細胞内外で多彩な機能を担っているリン脂質だが、その特徴的な極性基に関して、わずか数種類しか知られていない。申請者は、細胞は多くの種類の極性基を持つリン脂質が存在するはずと想定し、質量分析技術を利用した新規リン脂質の探索を開始した。その結果、幾つかの新規リン脂質を発見できた。この発見により、遺伝子・タンパク質から解析不可能だった、新しい生理現象の解明に繋がるだけでなく、脂質の変化により引き起こされる各種疾患発症機構の解明並びにその創薬標的の提示に貢献できる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (1 results)

  • [Int'l Joint Research] University of Michigan(米国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Attenuated cerebellar phenotypes in Inpp4a truncation mutants with preserved phosphatase activity.2023

    • Author(s)
      Tran DM, Yoshioka N, Bizen N, Mori-Ochiai Y, Yano M, Yanai S, Hasegawa J, Miyashita S, Hoshino M, Sasaki J, Sasaki T, Takebayashi H
    • Journal Title

      Dis Model Mech

      Volume: 16 Issue: 7 Pages: 192-206

    • DOI

      10.1242/dmm.050169

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of the ESCRT pathway and multivesicular bodies accelerates degradation of proteins associated with neurodegeneration2023

    • Author(s)
      Benyair Ron、Panapakkam Giridharan Sai Srinivas、Rivero-R?os Pilar、Hasegawa Junya、Bristow Emily、Eskelinen Eeva-Liisa、Shmueli Merav D、Fishbain-Yoskovitz Vered、Merbl Yifat、Sharkey Lisa M、Paulson Henry L.、Hanson Phyllis I、Patnaik Samarjit、Al-Ramahi Ismael、Botas Juan、Marugan Juan、Weisman Lois S.
    • Journal Title

      Autophagy Reports

      Volume: 2 Issue: 1 Pages: 2166722-2166722

    • DOI

      10.1080/27694127.2023.2166722

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their diseaseassociated regulation.2022

    • Author(s)
      Morioka S, Nakanishi H, Yamamoto T, Hasegawa J, Tokuda E, Hikita T, Sakihara T, Kugii Y, Oneyama C, Yamazaki M, Suzuki A, Sasaki J, Sasaki T.
    • Journal Title

      Nature Communications

      Volume: 13(1) Issue: 1 Pages: 83-83

    • DOI

      10.1038/s41467-021-27648-z

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity2022

    • Author(s)
      Hasegawa Junya、Tokuda Emi、Yao Yao、Sasaki Takehiko、Inoki Ken、Weisman Lois S.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 33 Issue: 3

    • DOI

      10.1091/mbc.e21-06-0309

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics2022

    • Author(s)
      Kaori Kanemaru, Makoto Shimozawa, Manabu Kitamata, Rikuto Furuishi, Hinako Kayano, Yui Sukawa, Yuuki Chiba, Takatsugu Fukuyama, Junya Hasegawa, Hiroki Nakanishi, Takuma Kishimoto, Kazuya Tsujita, Kazuma Tanaka, Toshiki Itoh, Junko Sasaki, Takehiko Sasaki, Kiyoko Fukami, Yoshikazu Nakamura
    • Journal Title

      Nature Communications

      Volume: - Issue: 1 Pages: 2347-2347

    • DOI

      10.1038/s41467-022-30061-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] イノシトールリン脂質が制御する老化メカニズムの解明2023

    • Author(s)
      長谷川純矢、佐々木純子、佐々木雄彦
    • Organizer
      第65回日本脂質生化学会
    • Related Report
      2023 Annual Research Report

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Published: 2022-07-05   Modified: 2025-01-30  

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