Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and aSNAP
- University of Texas Southwestern Medical Center, United States
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.
Article and author information
Author details
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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Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and aSNAP
eLife 8:e38880.
https://doi.org/10.7554/eLife.38880
