| 研究実績の概要 |
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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