Exploration of substrate proteins of calmodulin kinase II by using the kinase-dead knock-in mouse.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: YAMAGATA Yoko 生理学研究所, 助教 (20210338)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 蛋白質リン酸化 / キナーゼ / 学習・記憶 / 行動テスト

Outline of Final Research Achievements

To understand higher-order brain functions, especially learning and memory, and to contribute to the prevention and treatment of human diseases, molecular analyses of their mechanisms are essential. In this study, I made exploration of substrate proteins of calmodulin kinase IIα, one of the representative protein kinases in the brain that are indispensable for learning and memory, by using functionally modified, genetically engineered mice. At the same time, I showed that there is brain regional specificity in the molecular mechanisms of learning and memory, and made selection of appropriate behavioral memory tests for the evaluation of substrate proteins. These studies will be useful for further understanding of human brain functions and contribute to the prevention and treatment of human brain disorders.

Free Research Field

脳神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、蛋白質リン酸化酵素の基質蛋白質の探索にとって機能的遺伝子改変マウスの活用が有用であること、また、脳の機能的部位に特化した解析が重要であることが判明した。今後さらに探索した基質候補蛋白質の同定を進め、実際の生体における学習・記憶の時間的経過と共に、どのようにリン酸化状態が変化するのか、また病態とどのように関連するのかを明らかにすることにより、学習・記憶に障害を来すヒト疾患の予防・治療に貢献することが期待できる。