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Regulation of synaptic plasticity by heparan sulfate 6-O sulfatase (Sulf)

Research Project

Project/Area Number 18K06145
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 InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KAMIMURA Keisuke  公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, 主席研究員 (30529524)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsへパラン硫酸 / プロテオグリカン / ヘパラン硫酸6-O脱硫酸化酵素 / シナプス可塑性 / 自閉症 / シナプス / グルタミン酸受容体 / へパラン硫酸修飾酵素 / ショウジョウバエ / ヘパラン硫酸 / 精神疾患 / 神経筋接合部
Outline of Final Research Achievements

To investigate the role of fine structures of the heparan sulfate (HS) chains in synaptic plasticity, we focused on the neuromuscular junction of Drosophila, a model of glutamatergic synapses. In Drosophila, starvation is known to increase the number of synaptic terminals at the neuromuscular junction. However, it was found that the number of synaptic boutons did not increase in starved animals lacking the 6-O sulfatase (Sulf1) that desulfates the 6-O position of the HS chain. In addition, the starvation dependent increase of glutamate receptor GluRIIA was inhibited in Sulf1 mutants. These results suggest that fine structures of the HS chains regulate synaptic plasticity.

Academic Significance and Societal Importance of the Research Achievements

近年、ニューレキシンなどのHSPGに加え、いくつかのHS修飾酵素の変異が自閉症及び統合失調症の発症に関与することが報告されている。しかしながら、HS鎖の修飾異常がどのように影響することで疾患の発症に関与するのかはわかっていない。したがって、本研究においてHS修飾酵素によるシナプス可塑性調節機構を明らかにしたことは神経・精神疾患治癒を目標とした医学的研究においても極めて重要である。

Report

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

    (14 results)

All 2021 2020 2019 Other

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

  • [Journal Article] Roles of Glypican and Heparan Sulfate at the Synapses2021

    • Author(s)
      Kamimura Keisuke
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 33 Issue: 194 Pages: E85-E90

    • DOI

      10.4052/tigg.2017.1E

    • NAID

      130008068233

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2021-07-25
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of <i>Drosophila</i> germline stem cells2021

    • Author(s)
      Hayashi Yoshiki、Shibata Arisa、Kamimura Keisuke、Kobayashi Satoru
    • Journal Title

      Development, Growth &amp; Differentiation

      Volume: 63 Issue: 6 Pages: 295-305

    • DOI

      10.1111/dgd.12741

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glypicans and heparan sulfate in synaptic development. neural plasticity and neurological disorders.2021

    • Author(s)
      Keisuke Kamimura, Nobuaki Maeda
    • Journal Title

      Front. Neural Circuits

      Volume: 15 Pages: 595596-595596

    • DOI

      10.3389/fncir.2021.595596

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heparan sulfate chains of glypican and neurexin at the synapse2020

    • Author(s)
      神村圭亮
    • Journal Title

      生化学

      Volume: 92 Issue: 5 Pages: 740-743

    • DOI

      10.14952/SEIKAGAKU.2020.920740

    • NAID

      40022394520

    • ISSN
      0037-1017
    • Year and Date
      2020-10-25
    • Related Report
      2020 Research-status Report
  • [Journal Article] The HSPG Glypican Regulates Experience-dependent Synaptic and Behavioral Plasticity by Modulating the Non-canonical BMP Pathway.2019

    • Author(s)
      Keisuke Kamimura, Aiko Odajima, Yuko Ikegawa, Chikako Maru, and Nobuaki Maeda.
    • Journal Title

      Cell Reports

      Volume: 28 (12) Issue: 12 Pages: 3144-3156

    • DOI

      10.1016/j.celrep.2019.08.032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] シナプスの可塑的な形態変化におけるヘパラン硫酸微細構造の役割2021

    • Author(s)
      神村圭亮、小田嶋愛子、丸山千秋
    • Organizer
      第40回日本糖質学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] グリピカンは非古典的BMP経路を介して経験依存的なシナプスと行動の可塑性を調節する2019

    • Author(s)
      神村圭亮、小田嶋愛子、前田信明
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Drosophila glypican regulates experience-dependent synaptic and behavioral plasticity2019

    • Author(s)
      Keisuke Kamimura
    • Organizer
      Proteoglycan Future Leaders Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The HSPG Glypican Regulates Experience-dependent Synaptic and Behavioral Plasticity by Modulating the Non-canonical BMP Pathway.2019

    • Author(s)
      Keisuke Kamimura, Aiko Odajima, Nobuaki Maeda
    • Organizer
      11th International Conference on Proteoglycans
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] グリピカンは経験依存的なシナプスと行動の可塑性を調節する2019

    • Author(s)
      神村圭亮、小田嶋愛子、前田信明
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Research-status Report
  • [Remarks] 公益財団法人東京都医学総合研究所 脳神経回路形成プロジェクト

    • URL

      https://www.igakuken.or.jp/regeneration/

    • Related Report
      2021 Annual Research Report
  • [Remarks] (公財)東京都医学総合研究所 脳神経回路形成プロジェクト

    • URL

      https://www.igakuken.or.jp/project/detail/regeneration.html

    • Related Report
      2020 Research-status Report
  • [Remarks] (公財)東京都医学総合研究所、神経回路形成プロジェクト

    • URL

      http://www.igakuken.or.jp/regeneration/

    • Related Report
      2019 Research-status Report
  • [Remarks] 東京都医学総合研究所ホームページ

    • URL

      http://www.igakuken.or.jp/project/detail/regeneration.html

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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