A reciprocal-activation-within-a-kinase-effector-complex regulates formation and maintenance of memory

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02528
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kyoto University
• Principal Investigator: Saneyoshi Takeo 京都大学, 医学研究科, 准教授 (00556201)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: シナプス可塑性 / 記憶 / CaMKII / 分子間相互作用 / 酵素基質複合体 / アクチン細胞骨格

Outline of Final Research Achievements

Some of neuronal activity pattern can induce a persistent change in the efficacy of synaptic transmission, a phenomenon known as synaptic plasticity. One form of plasticity, long-term potentiation (LTP) has been extensively studied as the cellular basis of memory. In LTP, the potentiated synaptic transmission persists along with structural changes in the synapses. As a memory molecule, CaMKII has been attracted researchers for long time. However, it has not yet been understood how CaMKII is regulated during LTP. In this study, we found a new CaMKII regulation: reciprocal activation within a kinase effector complex (RAKEC) that is made between CaMKII and its effector protein, which is mediated by a persistent interaction between CaMKII and a pseudosubstrate sequence on Tiam1, resulting in reciprocal activation of these two molecules. Through the RAKEC mechanism, CaMKII can maintain memory as biochemical activity in a synapse-specific manner.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究により分子記憶の一つはCaMKIIとTiam1によって構成されるタンパク質間相互作用として存在する事を示した。CaMKIIは、Rac1活性化だけではなく、様々な情報伝達経路に関わっていることが知られており、今回のTiam1のみならず多くの分子との相互作用が予想される。CaMKIIはシナプスで非常に高い濃度で存在するため、CaMKIIが維持する情報がRAKECを形成する分子間相互作用である事が示唆される。今後は、分子記憶の個体レベルでの検証を続けるとともに、RAKECを新しい創薬ターゲットとした認知症などの新規治療法につなげていくことを期待している。