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Regulation mechanism of Glycosphingolipids metabolism by O-GlcNACylation

Research Project

Project/Area Number 18K06120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionNagoya University (2021-2022)
Kawasaki Medical School (2018-2020)

Principal Investigator

Go Shinji  名古屋大学, 糖鎖生命コア研究所, 特任准教授 (10458218)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords糖鎖 / 糖脂質 / シアル酸 / リソソーム / O-GlcNAc / スフィンゴ糖脂質 / O-GlcNAc修飾 / スフィンゴ脂質
Outline of Final Research Achievements

We have been analyzing the integrated regulatory mechanism of cellular glycosylation by "O-GlcNAcylation (addition of the sugar N-acetylglucosamine (GlcNAc) to serine/threonine residues of proteins)," a post-translational modification of intracellular (cytoplasmic and nuclear) proteins.
In this study, it was clarified for the first time that O-GlcNAcylation regulates the biosynthesis of glycolipids, the metabolism of sialic acid, a sugar important for glycans, and lysosomal functions involved in the catabolism (degradation) of glycans. These findings suggest that cells may use GlcNAc as a sensor to sense the status of cellular glycans and to control appropriate glycan metabolism in an integrated manner.

Academic Significance and Societal Importance of the Research Achievements

これまで、糖鎖の生合成、分解は個別に研究が進められてきた。今回、GlcNAcを中心として(特にO-GlcNAc化を介して)、細胞の糖鎖代謝が統合的に連動して制御されていることを見出した。
また、GlcNAcアナログを用いた、糖鎖発現制御に関しても道筋が得られており、創薬、研究ツール開発にもつながることが期待できる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2018

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] The Urinary Bladder is Rich in Glycosphingolipids Composed of Phytoceramides2022

    • Author(s)
      Watanabe Takashi、Suzuki Akemi、Ohira Shin、Go Shinji、Ishizuka Yuta、Moriya Takuya、Miyaji Yoshiyuki、Nakatsuka Tota、Hirata Keita、Nagai Atsushi、Matsuda Junko
    • Journal Title

      Journal of Lipid Research

      Volume: 63 Issue: 12 Pages: 100303-100303

    • DOI

      10.1016/j.jlr.2022.100303

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of O-Linked Glycoconjugates in the Nervous System2022

    • Author(s)
      Inokuchi Jin-Ichi、Go Shinji、Hirabayashi Yoshio
    • Journal Title

      Adv Neurobiol .

      Volume: 29 Pages: 95-116

    • DOI

      10.1007/978-3-031-12390-0_4

    • ISBN
      9783031123894, 9783031123900
    • Related Report
      2022 Annual Research Report
  • [Journal Article] Involvement of acid ceramidase in the degradation of bioactive N-acylethanolamines2021

    • Author(s)
      Tsuboi Kazuhito、Tai Tatsuya、Yamashita Ryouhei、Ali Hanif、Watanabe Takashi、Uyama Toru、Okamoto Yoko、Kitakaze Keisuke、Takenouchi Yasuhiro、Go Shinji、Rahman Iffat Ara Sonia、Houchi Hitoshi、Tanaka Tamotsu、Okamoto Yasuo、Tokumura Akira、Matsuda Junko、Ueda Natsuo
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

      Volume: 1866 Issue: 9 Pages: 158972-158972

    • DOI

      10.1016/j.bbalip.2021.158972

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduction in MIR-219 expression underlies cellular pathogenesis of oligodendrocytes in a mouse model of Krabbe disease.2021

    • Author(s)
      Inamura N, Go S, Watanabe T, Takase H, Takakura N, Nakayama A, Takebayashi H, Matsuda J, Enokido Y.
    • Journal Title

      Brain Pathology

      Volume: - Issue: 5 Pages: 12951-12951

    • DOI

      10.1111/bpa.12951

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] O-GlcNAc修飾を介したシアル酸代謝制御機構2018

    • Author(s)
      郷 慎司
    • Organizer
      日本生化学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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