Functional synergy between the Munc13 C-terminal C1 and C2 domains

Xiaoxia Liu, Alpay Burak Seven, Marcial Camacho, Victoria Esser, Junjie Xu, Thorsten Trimbuch, Bradley Quade, Lijing Su, Cong Ma, Christian Rosenmund, Josep Rizo

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Neurotransmitter release requires SNARE complexes to bring membranes together, NSF-SNAPs to recycle the SNAREs, Munc18-1 and Munc13s to orchestrate SNARE complex assembly, and Synaptotagmin-1 to trigger fast Ca2+-dependent membrane fusion. However, it is unclear whether Munc13s function upstream and/or downstream of SNARE complex assembly, and how the actions of their multiple domains are integrated. Reconstitution, liposome-clustering and electrophysiological experiments now reveal a functional synergy between the C1, C2B and C2C domains of Munc13-1, indicating that these domains help bridging the vesicle and plasma membranes to facilitate stimulation of SNARE complex assembly by the Munc13-1 MUN domain. Our reconstitution data also suggest that Munc18-1, Munc13-1, NSF, αSNAP and the SNAREs are critical to form a ‘primed’ state that does not fuse but is ready for fast fusion upon Ca2+ influx. Overall, our results support a model whereby the multiple domains of Munc13s cooperate to coordinate synaptic vesicle docking, priming and fusion.

Original languageEnglish (US)
Article numbere13696
JournaleLife
Volume5
Issue numberMAY2016
DOIs
StatePublished - May 23 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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