液-液相分離を介したシナプス恒常的可塑性の新規機構
Project/Area Number |
21K15188
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 46010:Neuroscience-general-related
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Research Institution | Kyoto University |
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) |
2021-04-01 – 2022-03-31
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Project Status |
Discontinued (Fiscal Year 2021)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | memory formation / synaptic plasticity / PSD / CaMKII / LLPS / Phase separation / Synapse / Homeostatic plasticity / Memory |
Outline of Research at the Start |
シナプスの可塑性には長期増強・長期抑圧および神経細胞全体の活動バランスを保つ恒常的可塑性が知られる。申請者らは液-液相分離現象によりシナプス内に活動依存的に形成される蛋白質集合体こそが、数多の蛋白質の動態を制御するシナプス可塑性の本質であると提案している。この蛋白質集合体には環境や刺激に応じて蛋白質の量と局在を自律的に制御する機能があるが、縮小を誘導しシナプス強度を負に調節する可能性のある因子としてCamk2n1/2遺伝子によりコードされる機能未知の小さな蛋白質がある。本研究ではCamk2n1/2の恒常的可塑性に果たす役割を遺伝学・生化学・細胞生物学の最先端の手法を用いて明らかにしていく。
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Outline of Annual Research Achievements |
To investigate the molecular mechanism underlying the memory formation, previously I found that a transient calcium signaling in specific synapses during learning forms permanent condensate of a set of synaptic proteins, including GluN2B, a subunit of NMDA receptor, Stargazin, auxiliary subunit of AMPA receptor, PSD-95 and Neuroligin-1 (NLGN1), a neuronal adhesion molecule, via the activation of calcium/calmodulin-dependent protein kinase (CaMKII). Also, I have demonstrated that applying the endogenous inhibitors of CaMKII, Camk2n1/2, to the CaMKII-mediated protein condensates disrupt the phase. Interestingly, when the condensate is newly formed, applying Camk2n1/2 only makes the phase shrink, however, when the condensate has been formed for a while, applying Camk2n1/2 breaks down the entire phase. In addition, while less dendritic spines were observed with Camk2n1/2 overexpressed in dissociated hippocampal cultures, increased and smaller spines were observed with knock-out Camk2n1/2. Taken all together, the different resistance to the Camk2n1/2 and the opposite observation of spine number and morphology might be involved in the mechanism for the turnover of synapses, which needs future experiments to clarify in this intriguing phenomenon.
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Report
(1 results)
Research Products
(1 results)