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-αSNAP, which can lead to de-priming. Here we show that trans-SNARE complex formation in the presence of NSF-αSNAP 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-αSNAP. 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.
| Original language | English (US) |
|---|---|
| Article number | e38880 |
| Journal | eLife |
| Volume | 8 |
| DOIs | |
| State | Published - Jan 18 2019 |
Keywords
- Munc13
- Munc18-1
- N-ethylmaleimide sensitive factor
- SNAREs
- alphaSNAP
- cell biology
- neuroscience
- neurotransmittersrelease
- none
ASJC Scopus subject areas
- Neuroscience(all)
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)