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v-SNARE transmembrane domains function as catalysts for vesicle fusion
Vesicle fusion is mediated by an assembly of SNARE proteins between opposing membranes, but it is unknown whether transmembrane domains (TMDs) of SNARE proteins serve mechanistic functions that go beyond passive anchoring of the force-generating SNAREpin to the fusing membranes. Here, we show that c...
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/PMC4972536/ https://www.ncbi.nlm.nih.gov/pubmed/27343350 http://dx.doi.org/10.7554/eLife.17571 |
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author | Dhara, Madhurima Yarzagaray, Antonio Makke, Mazen Schindeldecker, Barbara Schwarz, Yvonne Shaaban, Ahmed Sharma, Satyan Böckmann, Rainer A Lindau, Manfred Mohrmann, Ralf Bruns, Dieter |
author_facet | Dhara, Madhurima Yarzagaray, Antonio Makke, Mazen Schindeldecker, Barbara Schwarz, Yvonne Shaaban, Ahmed Sharma, Satyan Böckmann, Rainer A Lindau, Manfred Mohrmann, Ralf Bruns, Dieter |
author_sort | Dhara, Madhurima |
collection | PubMed |
description | Vesicle fusion is mediated by an assembly of SNARE proteins between opposing membranes, but it is unknown whether transmembrane domains (TMDs) of SNARE proteins serve mechanistic functions that go beyond passive anchoring of the force-generating SNAREpin to the fusing membranes. Here, we show that conformational flexibility of synaptobrevin-2 TMD is essential for efficient Ca(2+)-triggered exocytosis and actively promotes membrane fusion as well as fusion pore expansion. Specifically, the introduction of helix-stabilizing leucine residues within the TMD region spanning the vesicle’s outer leaflet strongly impairs exocytosis and decelerates fusion pore dilation. In contrast, increasing the number of helix-destabilizing, ß-branched valine or isoleucine residues within the TMD restores normal secretion but accelerates fusion pore expansion beyond the rate found for the wildtype protein. These observations provide evidence that the synaptobrevin-2 TMD catalyzes the fusion process by its structural flexibility, actively setting the pace of fusion pore expansion. DOI: http://dx.doi.org/10.7554/eLife.17571.001 |
format | Online Article Text |
id | pubmed-4972536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-49725362016-08-04 v-SNARE transmembrane domains function as catalysts for vesicle fusion Dhara, Madhurima Yarzagaray, Antonio Makke, Mazen Schindeldecker, Barbara Schwarz, Yvonne Shaaban, Ahmed Sharma, Satyan Böckmann, Rainer A Lindau, Manfred Mohrmann, Ralf Bruns, Dieter eLife Neuroscience Vesicle fusion is mediated by an assembly of SNARE proteins between opposing membranes, but it is unknown whether transmembrane domains (TMDs) of SNARE proteins serve mechanistic functions that go beyond passive anchoring of the force-generating SNAREpin to the fusing membranes. Here, we show that conformational flexibility of synaptobrevin-2 TMD is essential for efficient Ca(2+)-triggered exocytosis and actively promotes membrane fusion as well as fusion pore expansion. Specifically, the introduction of helix-stabilizing leucine residues within the TMD region spanning the vesicle’s outer leaflet strongly impairs exocytosis and decelerates fusion pore dilation. In contrast, increasing the number of helix-destabilizing, ß-branched valine or isoleucine residues within the TMD restores normal secretion but accelerates fusion pore expansion beyond the rate found for the wildtype protein. These observations provide evidence that the synaptobrevin-2 TMD catalyzes the fusion process by its structural flexibility, actively setting the pace of fusion pore expansion. DOI: http://dx.doi.org/10.7554/eLife.17571.001 eLife Sciences Publications, Ltd 2016-06-25 /pmc/articles/PMC4972536/ /pubmed/27343350 http://dx.doi.org/10.7554/eLife.17571 Text en © 2016, Dhara 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 | Neuroscience Dhara, Madhurima Yarzagaray, Antonio Makke, Mazen Schindeldecker, Barbara Schwarz, Yvonne Shaaban, Ahmed Sharma, Satyan Böckmann, Rainer A Lindau, Manfred Mohrmann, Ralf Bruns, Dieter v-SNARE transmembrane domains function as catalysts for vesicle fusion |
title | v-SNARE transmembrane domains function as catalysts for vesicle fusion |
title_full | v-SNARE transmembrane domains function as catalysts for vesicle fusion |
title_fullStr | v-SNARE transmembrane domains function as catalysts for vesicle fusion |
title_full_unstemmed | v-SNARE transmembrane domains function as catalysts for vesicle fusion |
title_short | v-SNARE transmembrane domains function as catalysts for vesicle fusion |
title_sort | v-snare transmembrane domains function as catalysts for vesicle fusion |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972536/ https://www.ncbi.nlm.nih.gov/pubmed/27343350 http://dx.doi.org/10.7554/eLife.17571 |
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