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Regulation of neuronal plasticity through AMPA receptor association by characteristic N-glycans

Research Project

Project/Area Number 17K15090
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionKyoto University

Principal Investigator

Morise Jyoji  京都大学, 医学研究科, 助教 (60755669)

Research Collaborator SUZUKI Kenichi  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
KeywordsAMPA型グルタミン酸受容体 / N型糖鎖 / 一分子イメージング法 / 一分子イメージング
Outline of Final Research Achievements

AMPA-type glutamate receptor (AMPAR) is an ionotropic channel that accumulates in neuronal synaptic regions and provides rapid excitatory transmission. Until now, I analyzed the glycan structure on GluA1, the major subunit of AMPAR, and found that the immature glycans (high-mannose type glycan) existed at several N-glycosylation sites and also the specific N-glycosylation site was not glycosylated at a constant rate. Meanwhile, it was still unknown how the characteristic N-glycosylation on AMPAR could affect the ability of tetramer formation. The purpose of this study is to analyze the functional significance of characteristic N-glycosylation on AMPAR on living cell membranes and clarify the influence on neuronal plasticity.

Academic Significance and Societal Importance of the Research Achievements

AMPARは記憶学習形成の基盤となる神経可塑性において中心的役割を担うことから、そのチャネル形成調節機構の解明は神経科学分野での重要課題の1つとなっている。本研究成果は四量体形成における糖鎖の重要性を示すものであり、その学術的意義は高いと考える。また、創薬においてAMPARはてんかんや統合失調症などの標的分子として注目されており、事実拮抗薬等が近年研究開発されている。本研究はチャネル形成能を糖鎖が制御することを示すものであり、AMPAR上の糖鎖が新たな創薬ターゲットとなることも期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Site-specific HNK-1 epitope on alternatively spliced fibronectin type-III repeats in tenascin-C promotes neurite outgrowth of hippocampal neurons through contactin-12019

    • Author(s)
      Nakamura Ayasa、Morise Jyoji、Yabuno-Nakagawa Keiko、Hashimoto Yuki、Takematsu Hiromu、Oka Shogo
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0210193-e0210193

    • DOI

      10.1371/journal.pone.0210193

    • NAID

      120006549324

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] N-glycosylation of the AMPA-type glutamate receptor regulates cell surface expression and tetramer formation affecting channel function2018

    • Author(s)
      Munal Babu Kandel, Saki Yamamoto, Ryosuke Midorikawa, Jyoji Morise, Yoshihiko Wakazono, Shogo Oka, Kogo Takamiya
    • Journal Title

      Journal of Neurochemistry

      Volume: 147 Issue: 6 Pages: 730-747

    • DOI

      10.1111/jnc.14565

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of human natural killer-1 (HNK-1) carbohydrate in neuronal plasticity and disease.2017

    • Author(s)
      Morise J, Takematsu H, Oka S.
    • Journal Title

      Biochim. Biophys. Acta.

      Volume: 1861 Issue: 10 Pages: 2455-2461

    • DOI

      10.1016/j.bbagen.2017.06.025

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Monomers of AMPA-type glutamate receptor subunits diffuse in and out of spines; unraveling by single-molecule tracking2019

    • Author(s)
      Jyoji Morise, Kenichi G.N. Suzuki, Ayaka Kitagawa, Yoshihiko Wakazono, Kogo Takamiya, Taka A. Tsunoyama, Hiromu Takematsu, Akihiro Kusumi, and Shogo Oka
    • Organizer
      BPS19 63nd Annual Meeting of the Biophysical Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経細胞膜表面上でAMPA型グルタミン酸受容体サブユニットは単量体で拡散し、 一過的に複合体を形成する2018

    • Author(s)
      森瀬 譲二、鈴木 健一、北川 英佳、楠見 明弘、竹松 弘、岡 昌吾
    • Organizer
      第65回日本生化学会近畿支部
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖尿病性腎症に伴う腎臓内の非硫酸化型HNK-1糖鎖発現変化の解析2018

    • Author(s)
      北野 仁望、森瀬 譲二、岡 昌吾
    • Organizer
      第58回日本臨床化学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HNK-1糖鎖はTenascin-CとContactin-1を介した神経軸索伸長を促進させる2018

    • Author(s)
      森瀬 譲二、中村 綾沙、竹松 弘、岡 昌吾
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] N型糖鎖欠損体によるAMPA型グルタミン酸受容体の機能解析2017

    • Author(s)
      森瀬 譲二、鈴木 健一、北川 英佳、山本 采季、竹内 祐介、楠見 明弘、竹松 弘、岡 昌吾
    • Organizer
      第18回関西グライコサイエンスフォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] N型糖鎖によるAMPA型グルタミン酸受容体の機能調節機構の解析2017

    • Author(s)
      森瀬 譲二、鈴木 健一、山本 采季、北川 英佳、高倉 大輔、川崎 ナナ、楠見 明弘、竹松 弘、岡 昌吾
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] ストレプトゾトシン誘導性腎機能障害マウスにおける非硫酸化型HNK-1糖鎖の発現解析2017

    • Author(s)
      北野 仁望、森瀬 譲二、岡 昌吾
    • Organizer
      第57回日本臨床化学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗MAG抗体ニューロパチーにおける抗体affinityの継時的変化と臨床経過の比較2017

    • Author(s)
      松井 太郎、濱田 征宏、桑原 基、森瀬 譲二、岡 昌吾、楠 進
    • Organizer
      第29回日本神経免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://oka-lab.hs.med.kyoto-u.ac.jp/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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