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Structures and functions of synaptic cleft compartments

Research Project

Project/Area Number 18K06471
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionKyoto Sangyo University

Principal Investigator

HAMA Chihiro  京都産業大学, 総合学術研究所, 科研費研究員 (50238052)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsシナプス間隙 / ニコチン性アセチルコリン受容体 / シナプス / Hig / Hasp / ショウジョウバエ / サプレッサー変異 / sequestering subunit / アセチルコリン受容体 / コリン作動性 / Sclamp / ナノコンパートメント / エンドサイトーシス
Outline of Final Research Achievements

When the nervous system functions in our bodies, synapses, which are connecting parts between two adjacent neurons, play its central roles. The gaps between the two neurons are called synaptic clefts. One neuron secretes neurotransmitters, which traverse the clefts and bind their receptors located on the other neuron, thus transmitting neural information. Our team, using Drosophila genetics, identified two proteins Hig and Hasp, both of which were located in the synaptic clefts of cholinergic synapses, and found that these proteins regulate the synaptic levels of nicotinic acetylcholine receptors (nAChRs) through interacting with particular subunits of the receptors. Notably, one of the subunits become a lethal factor when Hig is missing, which may provide insight into the development of therapies for the disorders associated with the loss of nAChR.

Academic Significance and Societal Importance of the Research Achievements

神経機能が発揮されるうえで中心的な役割を果たすシナプスについての研究は重要であり、実際に多くの研究が行われてきたが、神経伝達物質受容体の一つであるニコチン性アセチルコリン受容体のシナプスにおける局在制御機構は不明であった。今回のわれわれの研究により、その機構の一部を明らかにできたことは神経科学の発展にとって意義のあることである。また、今回の研究により、生理的に機能する受容体サブユニットの一つがシナプス間隙の状態によっては、シナプスの機能を欠損させることが判明しており、このことはヒトの神経変性疾患の発症機序の解明に新たな視点を加えるものである。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021 2020 2019 2018 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (5 results) Remarks (2 results)

  • [Journal Article] Control of Synaptic Levels of Nicotinic Acetylcholine Receptor by the Sequestering Subunit Dα5 and Secreted Scaffold Protein Hig2023

    • Author(s)
      Nakayama Minoru、Nishimura Osamu、Nishimura Yuhi、Kitaichi Miwa、Kuraku Shigehiro、Sone Masaki、Hama Chihiro
    • Journal Title

      The Journal of Neuroscience

      Volume: 43 Issue: 22 Pages: 3989-4004

    • DOI

      10.1523/jneurosci.2243-21.2023

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Control of synaptic levels of nicotinic acetylcholine receptor by the sequestering subunit Dalpha5 and secreted scaffold protein Hig2023

    • Author(s)
      Minoru Nakayama, Osamu Nishimura, Yuhi Nishimura, Miwa Kitaichi, Shigehiro Kuraku, Masaki Sone, and Chihiro Hama
    • Journal Title

      the Journal of Neuroscience

      Volume: in press

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] シナプス間隙のナノコンパートメント形成に関わるHig, Hasp, Sclamp間の相互作用2022

    • Author(s)
      北市三和、浜千尋、中山実
    • Organizer
      日本分子生物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] シナプス間隙のナノコンパートメント形成を制御する膜タンパク質Sclamp2021

    • Author(s)
      北市三和、西村勇飛、浜 千尋
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Synaptic levels of acetylcholine receptors are controlled by the internalizing subunit Da5 and synaptic cleft protein Hig in the Drosophila brain2020

    • Author(s)
      Yuhi Nishimura, Minoru Nakayama, Osamu Nishimura, Shigehiro Kuraku, Masaki Sone, Chihiro Hama
    • Organizer
      日本神経科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ショウジョウバエ脳におけるアセチルコリン受容体のシナプス局在量はシナプス間隙タンパク質Higと相互作用するDalpha5サブユニットにより抑制的に調節される2019

    • Author(s)
      西村勇飛、中山 実、西村 理、工樂 樹洋、曽根 雅紀、浜 千尋
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Synaptic cleft protein Hig inhibits endocytosis of an AchR subunit Da5 to regulate AchR clustering2018

    • Author(s)
      Nakayama M, Nishimura O, Kuraku S, Sone M, Hama C
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Remarks] 神経回路発生研究室ホームページ

    • URL

      http://www.cc.kyoto-su.ac.jp/~hama/homepage-j.html/toppu.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 京都産業大学生命科学部教員紹介

    • URL

      http://www.kyoto-su.ac.jp/faculty/professors/ls/hama-chihiro.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2025-01-30  

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