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Functional synergy between the Munc13 C-terminal C(1) and C(2) domains
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 Ca(2+)-dependent membrane fusion. However, it is unclear whether Munc13s function upstream a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927299/ https://www.ncbi.nlm.nih.gov/pubmed/27213521 http://dx.doi.org/10.7554/eLife.13696 |
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author | Liu, Xiaoxia Seven, Alpay Burak Camacho, Marcial Esser, Victoria Xu, Junjie Trimbuch, Thorsten Quade, Bradley Su, Lijing Ma, Cong Rosenmund, Christian Rizo, Josep |
author_facet | Liu, Xiaoxia Seven, Alpay Burak Camacho, Marcial Esser, Victoria Xu, Junjie Trimbuch, Thorsten Quade, Bradley Su, Lijing Ma, Cong Rosenmund, Christian Rizo, Josep |
author_sort | Liu, Xiaoxia |
collection | PubMed |
description | 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 Ca(2+)-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 C(1), C(2)B and C(2)C 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 Ca(2+) influx. Overall, our results support a model whereby the multiple domains of Munc13s cooperate to coordinate synaptic vesicle docking, priming and fusion. DOI: http://dx.doi.org/10.7554/eLife.13696.001 |
format | Online Article Text |
id | pubmed-4927299 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-49272992016-07-01 Functional synergy between the Munc13 C-terminal C(1) and C(2) domains Liu, Xiaoxia Seven, Alpay Burak Camacho, Marcial Esser, Victoria Xu, Junjie Trimbuch, Thorsten Quade, Bradley Su, Lijing Ma, Cong Rosenmund, Christian Rizo, Josep eLife Biophysics and Structural Biology 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 Ca(2+)-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 C(1), C(2)B and C(2)C 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 Ca(2+) influx. Overall, our results support a model whereby the multiple domains of Munc13s cooperate to coordinate synaptic vesicle docking, priming and fusion. DOI: http://dx.doi.org/10.7554/eLife.13696.001 eLife Sciences Publications, Ltd 2016-05-23 /pmc/articles/PMC4927299/ /pubmed/27213521 http://dx.doi.org/10.7554/eLife.13696 Text en © 2016, Liu et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biophysics and Structural Biology 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 C(1) and C(2) domains |
title | Functional synergy between the Munc13 C-terminal C(1) and C(2) domains |
title_full | Functional synergy between the Munc13 C-terminal C(1) and C(2) domains |
title_fullStr | Functional synergy between the Munc13 C-terminal C(1) and C(2) domains |
title_full_unstemmed | Functional synergy between the Munc13 C-terminal C(1) and C(2) domains |
title_short | Functional synergy between the Munc13 C-terminal C(1) and C(2) domains |
title_sort | functional synergy between the munc13 c-terminal c(1) and c(2) domains |
topic | Biophysics and Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927299/ https://www.ncbi.nlm.nih.gov/pubmed/27213521 http://dx.doi.org/10.7554/eLife.13696 |
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