Functional Synergy between the Munc13 C-terminal C1 and C2 domains
- University of Texas Southwestern Medical Center, United States
- Charité-Universitätsmedizin Berlin, Germany
- Huazhong University of Science and Technology, China
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.
Article and author information
Author details
Reviewing Editor
- Axel T Brunger, Stanford University, United States
Ethics
Animal experimentation: Animal welfare committees of Charité Medical University and the Berlin state government Agency for Health and Social Services approved all protocols for animal maintenance and experiments (license no. T 0220/09).
Version history
- Received: December 9, 2015
- Accepted: May 22, 2016
- Accepted Manuscript published: May 23, 2016 (version 1)
- Version of Record published: June 29, 2016 (version 2)
Copyright
© 2016, Liu 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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Functional Synergy between the Munc13 C-terminal C1 and C2 domains
eLife 5:e13696.
https://doi.org/10.7554/eLife.13696
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