Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and aSNAP

Eric A. Prinslow, Karolina P. Stepien, Yun Zu Pan, Junjie Xu, Josep Rizo

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Article numbere38880
JournaleLife
Volume8
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience

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