Elucidation of regulatory mechanism of liquid-liquid phase separation underlying synaptic plasticity
| Project/Area Number |
22KF0163
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| Project/Area Number (Other) |
21F21384 (2021-2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2021-2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Kyoto University (2023)
Nagoya University (2021-2022) |
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Principal Investigator |
劉 品吾 (2023) 京都大学, 医学研究科, 研究員 (60886563)
木下 専 (2021-2022) 名古屋大学, 理学研究科, 教授 (30273460)
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| Co-Investigator(Kenkyū-buntansha) |
LIU PIN-WU 名古屋大学, 理学(系)研究科(研究院), 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2023: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2022: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | synaptic plasticity / memory / phase separation / シナプス / シナプス伝達 / シナプス可塑性 / 液－液相分離 / シナプス後膜肥厚 / 樹状突起棘 / スパイン / 記憶 |
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| Outline of Research at the Start |
学習・記憶の素過程であるシナプスの情報伝達は、PSDと呼ばれる蛋白質の集合体により調節されており、PSDの大きさがシナプス強度に比例する。学習後や睡眠時などでは細胞全体のシナプスの恒常性と可塑性を維持するためにPSDが縮小し、シナプス強度が抑圧されるが、その分子機構は不明である。本研究ではCaMKNsによるPSDの離散がシナプス強度の抑圧を介して恒常性維持に寄与するという仮説を検証する。
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| Outline of Annual Research Achievements |
Our study aims to understand memory formation by investigating synaptic plasticity and liquid-liquid phase separation (LLPS). We previously identified a “CaMKII-mediated LLPS condensate” responsive to calcium stimulation, indicative of learning-like events. In this project, we found that dissociation of this LLPS condensate revealed a gradual loss of resistance to its disruptor, suggesting a role in synaptic transmission down-regulation. Additionally, we found an unfamiliar phosphorylation of NMDA-type glutamate receptors within this condensate, linking LLPS dynamics to synaptic protein modifications.
This discovery not only enhances our understanding of synaptic plasticity but also opens possibilities for exploring LLPS in other neurobiological processes. For example, follow-up studies can involve validating LLPS-mediated synaptic modulation using gene-editing tools, like CRISPR-Cas9 knock-in, with living cell and/or tissue cultures. Also, we can develop photoresponsible sensors based on these finding, that would enable us to directly manipulate the formation and dissociation of LLPS condensate. By doing so, we can advance our knowledge of memory formation and potentially identify therapeutic targets for memory-related disorders, like dementia.
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Report
(3 results)
Research Products
(8 results)
