The endosomal Q-SNARE, Syntaxin 7, defines a rapidly replenishing synaptic vesicle recycling pool in hippocampal neurons

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Doshisha University
• Principal Investigator: Yasunori Mori 同志社大学, 研究開発推進機構, 准教授 (80443042)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 神経 / シナプス / シナプス小胞 / 小胞輸送 / ライブイメージング / SNARE / カルシウム / アクチン

Outline of Final Research Achievements

Replenishment of readily releasable synaptic vesicles (SVs) with vesicles in the recycling pool is important for sustained transmitter release during repetitive stimulation. However, whether all SVs in the recycling pool are recruited for release with equal probability and speed is unknown. Here, using comprehensive optical imaging of various presynaptic endosomal SNARE proteins in cultured hippocampal neurons, we demonstrate that part of the recycling pool bearing the endosomal Q-SNARE, syntaxin 7 (Stx7), is preferentially mobilized for release during high-frequency repetitive stimulation. Recruitment of the SV pool marked with an Stx7-reporter requires actin polymerization, as well as activation of the Ca2+/calmodulin signaling pathway. Our data indicate that endosomal membrane fusion involving Stx7 forms rapidly replenishing vesicles essential for synaptic responses to high-frequency repetitive stimulation.

Free Research Field

神経生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として、これまでの研究では明らかにできなかったシナプス小胞プールを細分化する分子基盤を提唱し、シナプス前終末における神経伝達物質の多様な開口放出機構を明らかにすることができた。また、本研究により明らかになったシナプス小胞プールの違いを支える分子基盤は、一般的な小胞膜輸送に関わる基礎的な知見にも貢献することができた。本研究で得られた基礎的な知見は、シナプス伝達の異常が原因となる神経疾患に対する新しい治療戦略への波及が期待される。