Q-SNARE Syntaxin 7 confers actin-dependent rapidly replenishing synaptic vesicles upon high activity

Abstract

Replenishment of readily releasable synaptic vesicles (SVs) with vesicles in the recycling pool is important for sustained transmitter release during repetitive stimulation. Kinetics of replenishment and available pool size define synaptic performance. However, whether all SVs in the recycling pool are recruited for release with equal probability is unknown. Here, using comprehensive optical imaging for 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 the Stx7-reporter requires high intra-terminal Ca2+ concentrations and actin polymerization. Furthermore, disruption of Stx7 function by overexpressing the N-terminal domain selectively abolished this pool. Thus, our data indicate that endosomal membrane fusion involving Stx7 is essential for adaptation of synapses to respond high-frequency repetitive stimulation.