• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Regulatory mechanism of synaptic plasticity through liquid-liquid phase separation of CaMKII

Research Project

Project/Area Number 20K21462
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionKyoto University

Principal Investigator

HAYASHI Yasunori  京都大学, 医学研究科, 教授 (90466037)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsCaMKII / シナプス可塑性 / 液-液相分離 / AMPA型グルタミン酸受容体 / NMDA型グルタミン酸受容体 / 興奮性シナプス / PSD-95 / 液-液相分離 / シナプス後膜肥厚 / Ca2+/カルモジュリン依存性蛋白質キナーゼ
Outline of Research at the Start

CaMKIIのCa2+依存性液-液相分離がシナプス可塑性の根源たるメカニズムを担っているのではないかという発想に至った。そこで、本研究ではCaMKIIがCa2+により活性化されると他の蛋白質とLLPSを起こすことで、シナプス活動依存的なシナプス局所への蛋白質の移行と濃縮を起こすという新たな仮説を立てた。この実証のため、本研究を遂行していく。

Outline of Final Research Achievements

Humans built our civilization by memorizing knowledge and skills. We spend our daily lives memorizing the faces and events of our loved ones. Memory is a brain function that permanently stores information of temporary events, such as what we have seen or eaten. During this process, the molecules in the brain undergo certain changes that withstand their turnover over time beyond the lifetime of the molecules themselves. We have shown that proteins in the brain form condensates when stimulated during learning. The neurons are filled with water, but these aggregates spontaneously separate and assemble from the water in the neurons as if they were oil droplets floating on water. The molecules themselves remember their own locations, while allowing them to turnover. In this way, this mechanism allows us to retain their memories throughout our lives. We hope our finding leads to a better understanding and eventually to a treat neurological diseases such as Alzheimer's disease.

Academic Significance and Societal Importance of the Research Achievements

私たち人類は知識や技術を記憶することで文明を築き、大切な人の顔や出来事を記憶することで日常を過ごしています。この新発見の機構を応用することで、アルツハイマー病などの治療ができるのではないかと期待しています。記憶は人間を人間たらしめる最も重要な能力ですが、わかっていることは多くありません。加齢・病気・事故により記憶を失ってしまうことは、肉体の損傷と同じかあるいはもっと大きな悲しみを伴います。また、過去の悲しい記憶に囚われて前向きに生きられなくなることもあります。私たちは記憶形成の分子機構の研究を通じて、人間がより人間らしく生活できる世界を実現したいと願っています。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2021 Other

All Int'l Joint Research (4 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Remarks (3 results)

  • [Int'l Joint Research] IINS(フランス)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] HKUST(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] 香港科学技術大学(中国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] ボルドー大学(フランス)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Novel mechanism of synaptic plasticity mediated by CaMKII2021

    • Author(s)
      林 康紀、細川 智永、劉 品吾、實吉 岳郎
    • Journal Title

      生化学

      Volume: 93 Issue: 2 Pages: 191-202

    • DOI

      10.14952/SEIKAGAKU.2021.930191

    • ISSN
      0037-1017
    • Year and Date
      2021-04-25
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation2021

    • Author(s)
      Hosokawa Tomohisa、Liu Pin-Wu、Cai Qixu、Ferreira Joana S.、Levet Florian、Butler Corey、Sibarita Jean-Baptiste、Choquet Daniel、Groc Laurent、Hosy Eric、Zhang Mingjie、Hayashi Yasunori
    • Journal Title

      Nature Neuroscience

      Volume: not yet Issue: 6 Pages: 777-785

    • DOI

      10.1038/s41593-021-00843-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Liquid-Liquid Phase Separation in Physiology and Pathophysiology of the Nervous System2021

    • Author(s)
      Hayashi Yasunori、Ford Lenzie K.、Fioriti Luana、McGurk Leeanne、Zhang Mingjie
    • Journal Title

      The Journal of Neuroscience

      Volume: 41 Issue: 5 Pages: 834-844

    • DOI

      10.1523/jneurosci.1656-20.2020

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regulation of synaptic nanodomain by liquid?liquid phase separation: A novel mechanism of synaptic plasticity2021

    • Author(s)
      Liu Pin-Wu、Hosokawa Tomohisa、Hayashi Yasunori
    • Journal Title

      Current Opinion in Neurobiology

      Volume: 69 Pages: 84-92

    • DOI

      10.1016/j.conb.2021.02.004

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CaMKII activation persistently segregates postsynaptic pro- teins via liquid phase separation2021

    • Author(s)
      Hosokawa, T., Liu, P.-W., Cai, Q., Ferreira, J.S., Levet, F., Butler, C., Sibarita, J.B., Choquet, D., Groc, L., Hosy, E., et al.
    • Journal Title

      Nat. Neurosci., in press.

      Volume: -

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CaMKII の新しいシナプス可塑性機構2021

    • Author(s)
      林 康紀,細川 智永,劉 品吾,實吉 岳郎
    • Journal Title

      生化学

      Volume: 93

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Remarks] 記憶形成は水と油の関係から ―脳内での新しいタンパク質集積機構―

    • URL

      http://glutamate.med.kyoto-u.ac.jp/j/

    • Related Report
      2021 Annual Research Report
  • [Remarks] An oil-water relationship explains memory

    • URL

      http://glutamate.med.kyoto-u.ac.jp/e/index.php/An_oil-water_relationship_explains_memory_formation_-_A_new_protein_segregation_mechanism_in_the_brain

    • Related Report
      2021 Annual Research Report
  • [Remarks]

    • URL

      http://glutamate.med.kyoto-u.ac.jp/j/index.php/%E3%83%8B%E3%83%A5%E3%83%BC%E3%82%B9

    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi