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 journalArticle

31 Citations (Scopus)

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

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SNARE Proteins
Fusion reactions
Synaptotagmin I
Membrane Fusion
Synaptic Vesicles
Membranes
Liposomes
Electric fuses
Neurotransmitter Agents
Cluster Analysis
Cell membranes
Cell Membrane
C2 Domains

ASJC Scopus subject areas

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

Cite this

Liu, X., Seven, A. B., Camacho, M., Esser, V., Xu, J., Trimbuch, T., ... Rizo, J. (2016). Functional synergy between the Munc13 C-terminal C1 and C2 domains. eLife, 5(MAY2016), [e13696]. https://doi.org/10.7554/eLife.13696

Functional synergy between the Munc13 C-terminal C1 and C2 domains. / Liu, Xiaoxia; Seven, Alpay Burak; Camacho, Marcial; Esser, Victoria; Xu, Junjie; Trimbuch, Thorsten; Quade, Bradley; Su, Lijing; Ma, Cong; Rosenmund, Christian; Rizo, Josep.

In: eLife, Vol. 5, No. MAY2016, e13696, 23.05.2016.

Research output: Contribution to journalArticle

Liu, X, Seven, AB, Camacho, M, Esser, V, Xu, J, Trimbuch, T, Quade, B, Su, L, Ma, C, Rosenmund, C & Rizo, J 2016, 'Functional synergy between the Munc13 C-terminal C1 and C2 domains', eLife, vol. 5, no. MAY2016, e13696. https://doi.org/10.7554/eLife.13696
Liu X, Seven AB, Camacho M, Esser V, Xu J, Trimbuch T et al. Functional synergy between the Munc13 C-terminal C1 and C2 domains. eLife. 2016 May 23;5(MAY2016). e13696. https://doi.org/10.7554/eLife.13696
Liu, Xiaoxia ; Seven, Alpay Burak ; Camacho, Marcial ; Esser, Victoria ; Xu, Junjie ; Trimbuch, Thorsten ; Quade, Bradley ; Su, Lijing ; Ma, Cong ; Rosenmund, Christian ; Rizo, Josep. / Functional synergy between the Munc13 C-terminal C1 and C2 domains. In: eLife. 2016 ; Vol. 5, No. MAY2016.
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