Proteomic analysis with high spatiotemporal resolution at the synapse

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22439
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: Fukata Yuko 生理学研究所, 分子細胞生理研究領域, 准教授 (40416186)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: プロテオミクス / シナプス / タンパク質相互作用 / 界面活性剤

Outline of Final Research Achievements

Biological proteins do not function alone, but interact with a variety of proteins to perform their physiological functions. Disruption of these protein-protein interactions could cause dysfunction of the protein, sometimes causing diseases. Therefore, identifying the true protein-protein interactions with high spatiotemporal resolution is extremely important. In this study, we selected the epilepsy-related proteins, ADAM22 and LGI1, and the enzymes that regulate protein localization as model proteins. We succeeded to identify novel protein-protein interactions which occur in the insoluble synaptic fraction and transiently occur in cells.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

シナプス不溶性画分からタンパク質複合体を可溶化、精製可能な実験条件（界面活性剤の種類と濃度）を確立し、脳シナプス膜画分におけるてんかん関連タンパク質ADAM22を含む複合体を網羅的、特異的に同定することに成功した。また、リン酸化修飾に関連した一過的なタンパク質相互作用を明らかにすることに成功した。このように、新たなタンパク質複合体の精製技術を開発することにより、これまで見過されてきたタンパク質相互作用を明らかにして、シナプス制御機構やてんかん病態の理解につながる成果を得た。