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| Content Provider | PubMed Central |
|---|---|
| Author | Liu, Xiaoxia Seven, Alpay Burak Camacho, Marcial Esser, Victoria Xu, Junjie Thorsten, Trimbuch Quade, Bradley Su, Lijing Cong, Ma Rosenmund, Christian Rizo, Josep |
| Editor | Brunger, Axel T. |
| Copyright Year | 2016 |
| 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. |
| Related Links | http://dx.doi.org/10.7554/elife.13696 |
| Starting Page | 13696 |
| File Format | |
| ISSN | 2050084X |
| e-ISSN | 2050084X |
| Journal | eLife |
| Volume Number | 5 |
| Language | English |
| Publisher | eLife Sciences Publications, Ltd |
| Publisher Date | 2016-05-01 |
| Access Restriction | Open |
| Rights Holder | eLife Sciences Publications, Ltd |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology |
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