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Demonstration of the vertebrate CMP-sialic acid synthetase as a novel regulatory protein of neural cell apoptosis

Research Project

Project/Area Number 21K15040
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionNagoya University

Principal Investigator

Wu Di  名古屋大学, 糖鎖生命コア研究所, 助教 (10817547)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsCMP-Sia synthetase / apoptosis / medaka fish / Apoptosis / Sialylation / CSS / neurogenesis / medaka / Sia-glycoconjugates
Outline of Research at the Start

CMP-sialic acid synthetase (CSS) is a key enzyme for the expression of Sia-Glycolconjugates on the cell surface. Our previous results suggest that CSS plays a critical role in neurogenesis, not only as a sialylation-involved enzyme but also as an apoptosis-related protein. To clarify how CSS regulates the neural cell apoptosis: (1) To identify protein X by the proximity labeling technique; (2) To characterize the interaction between protein X and CSS at the molecular level; (3) To clarify the significance of the protein X-CSS interaction at the animal level using medaka model.

Outline of Final Research Achievements

CMP-sialic acid synthetase (CSS) is a key enzyme in sialic acid metabolism. However, medaka with a point mutation in the N-domain of CSS (named MuN) were lethal at early developmental stage due to cardiomyopathy and abnormal apoptosis in neural cells without affecting the sialylation state. To clarify the mechanism, we studied on the interacting proteins of CSS in mouse neuroblastoma cell line (Neuro2A). As a result, various interacting proteins of CSS in Neuro2A cell were confirmed, including Fragile X related protein (FXRP), which is the key protein caused apoptosis in MuN medaka.

Academic Significance and Societal Importance of the Research Achievements

MuN mutant medaka is a perfect model, since it showed abnormal apoptosis in neural system and cardiomyopathy. It is also the first time to target on the interacting proteins of CSS. This study is important to understand the pathophysiological mechanism of Sia metabolism-related diseases.

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (16 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (8 results)

  • [Journal Article] Forced expression of α2,3-sialyltransferase IV rescues impaired heart development in α2,6-sialyltransferase I-deficient medaka.2023

    • Author(s)
      Takayuki Omoto, Di Wu, Emi Maruyama, Katsue Tajima, Masaya Hane, Chihiro Sato, Ken Kitajima
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 649 Pages: 62-70

    • DOI

      10.1016/j.bbrc.2023.01.010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Critical Role of the Cortical Alveolus Protease Alveolin in Chorion Hardening In Vivo at Medaka Fertilization.2023

    • Author(s)
      Fu B, Wu D, Yasumasu S, Hane M, Sato C, Kitajima K.
    • Journal Title

      Biomolecules

      Volume: 10;13(1) Issue: 1 Pages: 146-146

    • DOI

      10.3390/biom13010146

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and characterization of a deaminoneuraminic acid (Kdn)-specific aldolase from Sphingobacterium species2022

    • Author(s)
      Nakagawa Takahiro、Iwaki Yuya、Wu Di、Hane Masaya、Sato Chihiro、Kitajima Ken
    • Journal Title

      Glycobiology

      Volume: 33 Issue: 1 Pages: 47-56

    • DOI

      10.1093/glycob/cwac053

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel C-domain-dependent inhibition of the rainbow trout CMP-sialic acid synthetase activity by CMP-deaminoneuraminic acid2022

    • Author(s)
      Wu Di、Pierre-Andre Gilormini、Toda Sakura、Biot Christophe、Cedric Lion、Yann Guerardel、Sato Chihiro、Kitajima Ken
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 617 Pages: 16-21

    • DOI

      10.1016/j.bbrc.2022.05.031

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The α2,8-sialyltransferase 6 (St8sia6) localizes in the ER and enhances the anchorage-independent cell growth in cancer2022

    • Author(s)
      Hatanaka Rina、Araki Erino、Hane Masaya、Go Shiori、Wu Di、Kitajima Ken、Sato Chihiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 608 Pages: 52-58

    • DOI

      10.1016/j.bbrc.2022.03.146

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polysialylation in a DISC1 Mutant Mouse2022

    • Author(s)
      Takahashi Yuka、Abe Chikara、Hane Masaya、Wu Di、Kitajima Ken、Sato Chihiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 9 Pages: 5207-5207

    • DOI

      10.3390/ijms23095207

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sulfation of sialic acid is ubiquitous and essential for vertebrate development2022

    • Author(s)
      Ertunc Nursah、Phitak Thanyaluck、Wu Di、Fujita Hiroshi、Hane Masaya、Sato Chihiro、Kitajima Ken
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 12496-12496

    • DOI

      10.1038/s41598-022-15143-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A point-mutation in the C-domain of CMP-sialic acid synthetase leads to lethality of medaka due to protein insolubility2021

    • Author(s)
      Wu Di、Arakawa Hiromu、Fujita Akiko、Hashimoto Hisashi、Hibi Masahiko、Naruse Kiyoshi、Kamei Yasuhiro、Sato Chihiro、Kitajima Ken
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 23211-23211

    • DOI

      10.1038/s41598-021-01715-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] The novel functions of N-domain and C-domain of CMP-sialic acid synthetase at organism level2022

    • Author(s)
      Di Wu, Hisashi Hashimoto, Masahiko Hibi,Yasuhiro Kamei, Kiyoshi Naruse, Chihiro Sato, Ken Kitajima
    • Organizer
      Sialoglyco2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] A point-mutation in the N-domain of CMP-sialic acid synthetase leads to abnormal apoptosis in medaka2022

    • Author(s)
      Di Wu, Hisashi Hashimoto, Masahiko Hibi, Yasuhiro Kamei, Chihiro Sato, Ken Kitajima
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] A point-mutation in N-domain of CMP-sialic acid synthetase induced abnormal apoptosis in medaka2022

    • Author(s)
      Di Wu, Hisashi Hashimoto, Masahiko Hibi, Kiyoshi Naruse, Yasuhiro Kamei, Chihiro Sato, Ken Kitajima
    • Organizer
      第42回 日本糖質学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] An impairment of the C-domain of CMP-sialic acid synthetase causes lethality of medaka due to protein insolubility2022

    • Author(s)
      Di Wu, Chihiro Sato, Ken Kitajima
    • Organizer
      日本農芸化学会の2022年度大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] C-domain of CMP-sialic acid synthetase is important to the enzymatic stability, which is essential for the early development of medaka fish2021

    • Author(s)
      Di Wu, Akiko Fujita, Hisashi Hashimoto, Masahiko Hibi, Kiyoshi Naruse, Yasuhiro Kamei, Chihiro Sato, Ken Kitajima
    • Organizer
      The 27th Japanese Medaka and Zebrafish Meeting
    • Related Report
      2021 Research-status Report
  • [Presentation] The C-domain of CMP-sialic acid synthetase is important for the enzymatic stability, which is essential for the survival of medaka fish2021

    • Author(s)
      Di Wu, Akiko Fujita, Hisashi Hashimoto, Masahiko Hibi, Kiyoshi Naruse, Yasuhiro Kamei, Chihiro Sato, Ken Kitajima
    • Organizer
      第41回 日本糖質学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] The stability of CMP-sialic acid synthetase was impaired by a point-mutation in the C-domain, which leads to lethality of medaka2021

    • Author(s)
      Di Wu, Akiko Fujita, Hisashi Hashimoto, Masahiko Hibi, Kiyoshi Naruse, Yasuhiro Kamei, Chihiro Sato, Ken Kitajima
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Sialylation plays critical roles in embryogenesis in medaka2021

    • Author(s)
      Di Wu, Akiko Fujita, Hisashi Hashimoto, Masahiko Hibi, Yoshihito Taniguchi, Yasuhiro Kamei, Chihiro Sato, Ken Kitajima
    • Organizer
      日本農芸化学会の2021年度大会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2024-01-30  

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