Molecular mechanisms of signaling molecule condensation by liquid-liquid phase separation for memory maintenance

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21463
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Kyoto University
• Principal Investigator: Saneyoshi Takeo 京都大学, 医学研究科, 准教授 (00556201)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 生物学的相分離 / CaMKII / アクチン細胞骨格 / リン酸化酵素

Outline of Final Research Achievements

CaMKII and the Rho family signaling molecules underwent phase separation We have been performed in vitro reconstitution experiments with CaMKII, Pak1, LIMK1, Tiam1, betaPIX, and GIT1. We found that these proteins were phase-separated by which activated CaMKII phosphorylated them. FRET observation of the interaction between CaMKII, LIMK1 and Pak1 during LTP induction in hippocampal neurons revealed an increase in the interaction at the synapse in response to stimulation. In the future, we plan to verify whether the synaptic interactions are mediated by the liquid-liquid phase-separation.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、記憶の長期保持をCaMKIIの相分離の観点からアプローチしたものである。CaMKIIの変異がヒトの知的能力障害や自閉症の家系に見つかり、記憶障害などの病理にも関わることがわかってきた。Rhoファミリーシグナル分子も発達障害などとの関連が見つかっており、これらの情報伝達経路が一つにつながる可能性が出てきた。つまり、CaMKIIが引き起こす相分離による長期記憶形成および維持の理解は、基礎生物学のみならず臨床医学や創薬の観点からも非常に重要である。