PMID- 34408265 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20211214 IS - 2399-3642 (Electronic) IS - 2399-3642 (Linking) VI - 4 IP - 1 DP - 2021 Aug 18 TI - The endosomal Q-SNARE, Syntaxin 7, defines a rapidly replenishing synaptic vesicle recycling pool in hippocampal neurons. PG - 981 LID - 10.1038/s42003-021-02512-4 [doi] LID - 981 AB - Upon the arrival of repetitive stimulation at the presynaptic terminals of neurons, replenishment of readily releasable synaptic vesicles (SVs) with vesicles in the recycling pool is important for sustained neurotransmitter release. Kinetics of replenishment and the available pool size define synaptic performance. However, whether all SVs in the recycling pool are recruited for release with equal probability and speed is unknown. Here, based on comprehensive optical imaging of various presynaptic endosomal SNARE proteins in cultured hippocampal neurons, all of which are implicated in organellar membrane fusion in non-neuronal cells, we show 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 Ca(2+)/calmodulin signaling pathway, reminiscent of rapidly replenishing SVs characterized previously in calyx of Held synapses. Furthermore, disruption of Stx7 function by overexpressing its N-terminal domain selectively abolished this pool. Thus, our data indicate that endosomal membrane fusion involving Stx7 forms rapidly replenishing vesicles essential for synaptic responses to high-frequency repetitive stimulation, and also highlight functional diversities of endosomal SNAREs in generating distinct exocytic vesicles in the presynaptic terminals. CI - (c) 2021. The Author(s). FAU - Mori, Yasunori AU - Mori Y AD - Laboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto, Japan. yasmori@yamanashi.ac.jp. AD - Department of Biochemistry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. yasmori@yamanashi.ac.jp. FAU - Takenaka, Koh-Ichiro AU - Takenaka KI AD - Laboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto, Japan. FAU - Fukazawa, Yugo AU - Fukazawa Y AUID- ORCID: 0000-0001-7436-8797 AD - Division of Brain Structure and Function, Research Center for Child Mental Development, Life Science Innovation Center, School of Medical Science, University of Fukui, Fukui, Japan. FAU - Takamori, Shigeo AU - Takamori S AD - Laboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto, Japan. stakamor@mail.doshisha.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210818 PL - England TA - Commun Biol JT - Communications biology JID - 101719179 RN - 0 (Qa-SNARE Proteins) SB - IM MH - Animals MH - Endosomes/*metabolism MH - Hippocampus/*metabolism MH - Mice MH - Mice, Inbred ICR MH - Neurons/*metabolism MH - Qa-SNARE Proteins/*metabolism MH - Synaptic Vesicles/*metabolism PMC - PMC8373932 COIS- The authors declare no competing interests. EDAT- 2021/08/20 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/08/18 CRDT- 2021/08/19 06:30 PHST- 2020/08/22 00:00 [received] PHST- 2021/08/02 00:00 [accepted] PHST- 2021/08/19 06:30 [entrez] PHST- 2021/08/20 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/08/18 00:00 [pmc-release] AID - 10.1038/s42003-021-02512-4 [pii] AID - 2512 [pii] AID - 10.1038/s42003-021-02512-4 [doi] PST - epublish SO - Commun Biol. 2021 Aug 18;4(1):981. doi: 10.1038/s42003-021-02512-4.