Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and aSNAP
Abstract
Neurotransmitter release requires formation of trans-SNARE complexes between the synaptic vesicle and plasma membranes, which likely underlies synaptic vesicle priming to a release-ready state. It is unknown whether Munc18-1, Munc13-1, complexin-1 and synaptotagmin-1 are important for priming because they mediate trans-SNARE complex assembly and/or because they prevent trans-SNARE complex disassembly by NSF-aSNAP, which can lead to de-priming. Here we show that trans-SNARE complex formation in the presence of NSF-aSNAP requires both Munc18-1 and Munc13-1, as proposed previously, and is facilitated by synaptotagmin-1. Our data also show that Munc18-1, Munc13-1, complexin-1 and likely synaptotagmin-1 contribute to maintaining assembled trans-SNARE complexes in the presence of NSF-aSNAP. We propose a model whereby Munc18-1 and Munc13-1 are critical not only for mediating vesicle priming but also for precluding de-priming by preventing trans-SNARE complex disassembly; in this model, complexin-1 also impairs de-priming, while synaptotagmin-1 may assist in priming and hinder de-priming.
Data availability
Representative examples of all the data generated and analyzed during this study are included in the manuscript and supporting files.
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Funding
National Institute of Neurological Disorders and Stroke (R35 NS097333)
- Josep Rizo
Welch Foundation (I-1304)
- Josep Rizo
National Institute of General Medical Sciences (T32 GM008297)
- Eric A Prinslow
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Prinslow et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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