Analyzing the Spatiotemporal Dynamics of Syntaxin in the Exocytosis Process of Synaptic Vesicles

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Namiki Shigeyuki 東京大学, 大学院医学系研究科(医学部), 講師 (90452193)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: シナプス分子 / 一分子蛍光追跡技術

Outline of Final Research Achievements

Understanding the spatiotemporal dynamics of syntaxin and related synaptic molecules on the cell membrane, which control the exocytosis process of synaptic vesicles, is necessary for elucidating the control mechanisms of synaptic transmission efficiency. In this study, we analyzed the spatiotemporal dynamics of Tarp-γ8, which controls the localization of AMPA-type receptors in cooperation with PSD-95, using the fluorescence regeneration-based fluorescence labeling technique called DeQODE tagging. We used COS7 cells as a model system, where PSD-95 clusters were formed, and revealed that the movement of Tarp-γ8 is restricted by its interaction with PSD-95 clusters. Furthermore, we demonstrated that Tarp-γ8 could transition between a stationary state and a more mobile state on the PSD-95 cluster.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究はシナプス伝達効率の制御機構を解明することによって脳の機能に関する重要な知見を提供し、神経変性疾患の病態解明や治療法の開発への貢献が見込まれる。さらに、本研究の成果は神経系疾患の治療において革新的なアプローチを提供し、新たな治療戦略の開発にもつながる可能性があります。また、シナプス分子の時空間ダイナミクスに関連する特定のタンパク質や相互作用の特定により、薬物開発にも応用され、神経系疾患の治療薬の開発に寄与することが期待できる。