2023 Fiscal Year Annual Research Report
シナプス可塑性の基盤となる液-液相分離制御機構の解明
| Project/Area Number |
22KF0163
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| Allocation Type | Multi-year Fund |
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| Research Institution | Kyoto University |
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Principal Investigator |
劉 品吾 京都大学, 医学研究科, 研究員 (60886563)
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Keywords | synaptic plasticity / memory / phase separation |
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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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