Regulatory mechanism of synaptic plasticity through liquid-liquid phase separation of CaMKII
| Project/Area Number |
20K21462
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 46:Neuroscience and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| Keywords | CaMKII / 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 |
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| 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。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(13 results)
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[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.
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Journal Title
Nat. Neurosci., in press.
Volume: -
Related Report
Peer Reviewed / Int'l Joint Research
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