| Project/Area Number |
17K14947
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurophysiology / General neuroscience
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | シナプス可塑性 / synaptic plasticity / learning and memory / synaptic structure |
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| Outline of Final Research Achievements |
To examine the role of CaMKII for postsynaptic density (PSD), the activity of CaMKII was observed by FRET technology at PSD. We found that actually around half of CaMKII is already active. Its downstream substrates are also already phosphorylated and decreased by CaMKII inhibitor. We tried non-biased identification for CaMKII interactor and we got many candidates including known substrates and interactor.
To examine the significance of this interaction, we tried artificial PSD as the collaboration with Prof. Zhang, HongKong University Science and Technology. Using this method, we can make PSD like structure under microscope. Activation of CaMKII by adding calcium ion resulted in the expansion of artificial PSD. This result strongly suggests the structural role of CaMKII.
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| Academic Significance and Societal Importance of the Research Achievements |
シナプス可塑性の分子メカニズムは、これまでのCaMKIIの活性化によるAMPA受容体のリン酸化というモデルが複数の論文によって覆され、新たなモデルを提案する必要があった。本研究では、CaMKIIの酵素活性よりもその構造的役割に注目している。本研究によるとCaMKIIはカルシウムに反応しPSDにリクルートされ、その12量体で様々な蛋白質を繋ぎ留めることでシナプスタンパク質の量を増加させ、ひいては長期増強を実現している。このことは、CaMKIIの高すぎる発現量や特徴的な12量体構造の謎を解決するとともに、シナプス可塑性及び学習機構の新たなモデルを提唱するものである。
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