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Mechanisms for regulation of glycosylphosphatidylinositol biosynthesis

Research Project

Project/Area Number 21H02415
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionOsaka University

Principal Investigator

Kinoshita Taroh  大阪大学, 微生物病研究所, 特任教授(常勤) (10153165)

Co-Investigator(Kenkyū-buntansha) 村上 良子  大阪大学, 微生物病研究所, 特任教授 (00304048)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
KeywordsGPIアンカー / グリコシルホスファチジルイノシトール
Outline of Research at the Start

グリコシルホスファチジルイノシトール (GPIと略記) はヒト細胞表面に存在する160種類余のタンパク質に結合し、細胞膜アンカーとして機能する。GPIはタンパク質に結合しないフリーの糖脂質としても存在する。本研究では未だ理解が進んでいないGPI生合成の量の制御機構、GPI中間体の細胞質側から内腔側へのフリップのメカニズム、フリーGPIの実態と細胞内動態の解明を進め、制御機構を含めたGPI生合成の完全理解を目指す。

Outline of Final Research Achievements

This research project aimed to achieve three goals: 1) Understanding how GPI biosynthesis is upregulated; 2) Characterization of protein(s) involved in translocation of the second GPI biosynthetic intermediate from the cytoplasmic side to the luminal side of the endoplasmic reticulum membrane; 3) Characterization of un-linked free GPIs and intracellular trafficking of free GPI and GPI intermediates. For goal 1, we found accumulated precursors of specific GPI-anchored proteins, such as CD55 and CD48, upregulate GPI biosynthesis together with ARV1. For goal 2, we identified CLPTM1L as a lipid scramblase that is involved in transmembrane translocation of the second GPI intermediate, glucosamine-phosphatidylinositol. For goal 3, we characterized intracellular trafficking of free GPIs and various GPI biosynthetic intermediates.

Academic Significance and Societal Importance of the Research Achievements

GPIの生合成は形態形成、生体防御、神経系形成、受精などに必須であり、GPI生合成の欠損は先天性グリコシルホスファチジルイノシトール(GPI)欠損症や発作性夜間ヘモグロビン尿症といった重篤な疾患を引き起こす。GPI生合成に関する徹底した研究は、生体の生理と病理の理解に重要である。本研究により得られた、GPI生合成量の制御機構に関する成果やGPI生合成中間体とフリーGPIの細胞内動態に関する成果は、GPI生合成とGPI欠損症に関わる知見を一層深化させることにより生体の生理と病理の理解に資する。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (13 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (4 results) Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 8 results)

  • [Int'l Joint Research] Chinese Academy of Sciences/Jiangnan University(中国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Nationwide Hospital(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 江南大学(中国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] 江南大学(中国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] AAV-based gene therapy ameliorated CNS-specific GPI defect in mouse models2024

    • Author(s)
      Murakami Yoshiko、Umeshita Saori、Imanishi Kae、Yoshioka Yoshichika、Ninomiya Akinori、Sunabori Takehiko、Likhite Shibi、Koike Masato、Meyer Kathrin C.、Kinoshita Taroh
    • Journal Title

      Molecular Therapy - Methods & Clinical Development

      Volume: 32 Issue: 1 Pages: 101176-101176

    • DOI

      10.1016/j.omtm.2023.101176

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of lipid scramblases in regulating lipid distributions at cellular membranes2023

    • Author(s)
      Wang Yicheng、Kinoshita Taroh
    • Journal Title

      Biochemical Society Transactions

      Volume: 51 Issue: 5 Pages: 1857-1869

    • DOI

      10.1042/bst20221455

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Accumulated precursors of specific GPI-anchored proteins upregulate GPI biosynthesis with ARV1.2023

    • Author(s)
      Liu, Y.-S., Y. Wang, X. Zhou, L. Zhang, X.-D. Gao, Y. Murakami, M. Fujita and T. Kinoshita.
    • Journal Title

      J. Cell Biol.

      Volume: 222 Issue: 5 Pages: 1-20

    • DOI

      10.1083/jcb.202208159

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A point mutation in GPI-attachment signal peptide accelerates the development of prion disease2023

    • Author(s)
      Kobayashi Atsushi、Hirata Tetsuya、Shimazaki Taishi、Munesue Yoshiko、Aoshima Keisuke、Kimura Takashi、Nio-Kobayashi Junko、Hasebe Rie、Takeuchi Atsuko、Matsuura Yuichi、Kusumi Satoshi、Koga Daisuke、Iwasaki Yasushi、Kinoshita Taroh、Mohri Shirou、Kitamoto Tetsuyuki
    • Journal Title

      Acta Neuropathologica

      Volume: 145 Issue: 5 Pages: 637-650

    • DOI

      10.1007/s00401-023-02553-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequential hydrolysis of FAD by ecto-5′ nucleotidase CD73 and alkaline phosphatase is required for uptake of vitamin B2 into cells2022

    • Author(s)
      Shichinohe Natsuki、Kobayashi Daisuke、Izumi Ayaka、Hatanaka Kazuya、Fujita Rio、Kinoshita Taroh、Inoue Norimitsu、Hamaue Naoya、Wada Keiji、Murakami Yoshiko
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 12 Pages: 102640-102640

    • DOI

      10.1016/j.jbc.2022.102640

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis2022

    • Author(s)
      Wang Yicheng、Menon Anant K.、Maki Yuta、Liu Yi-Shi、Iwasaki Yugo、Fujita Morihisa、Guerrero Paula A.、Silva Daniel Varon、Seeberger Peter H.、Murakami Yoshiko、Kinoshita Taroh
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 14 Pages: 7211-7211

    • DOI

      10.1073/pnas.2115083119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ethanolamine‐phosphate on the second mannose is a preferential bridge for some GPI‐anchored proteins2022

    • Author(s)
      Ishida Mizuki、Maki Yuta、Ninomiya Akinori、Takada Yoko、Campeau Philippe、Kinoshita Taroh、Murakami Yoshiko
    • Journal Title

      EMBO reports

      Volume: 23 Issue: 7

    • DOI

      10.15252/embr.202154352

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rescue of Glycosylphosphatidylinositol-Anchored Protein Biosynthesis Using Synthetic Glycosylphosphatidylinositol Oligosaccharides2021

    • Author(s)
      Guerrero Paula A.、Murakami Yoshiko、Malik Ankita、Seeberger Peter H.、Kinoshita Taroh、Varon Silva Daniel
    • Journal Title

      ACS Chemical Biology

      Volume: 16 Issue: 11 Pages: 2297-2306

    • DOI

      10.1021/acschembio.1c00465

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential use of p24 family members as cargo receptors for the transport of glycosylphosphatidylinositol-anchored proteins and Wnt12021

    • Author(s)
      Tashima Yuko、Hirata Tetsuya、Maeda Yusuke、Murakami Yoshiko、Kinoshita Taroh
    • Journal Title

      The Journal of Biochemistry

      Volume: 171 Issue: 1 Pages: 75-83

    • DOI

      10.1093/jb/mvab108

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed

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Published: 2021-04-28   Modified: 2025-01-30  

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