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...
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doaj-1e959e37992f4c52b003f93e4f9c82132021-05-05T00:27:25ZengeLife Sciences Publications LtdeLife2050-084X2016-06-01510.7554/eLife.17571v-SNARE transmembrane domains function as catalysts for vesicle fusionMadhurima Dhara0Antonio Yarzagaray1Mazen Makke2Barbara Schindeldecker3Yvonne Schwarz4Ahmed Shaaban5Satyan Sharma6Rainer A Böckmann7https://orcid.org/0000-0002-9325-5162Manfred Lindau8Ralf Mohrmann9Dieter Bruns10https://orcid.org/0000-0002-2497-1878Institute for Physiology, Saarland University, Homburg, GermanyInstitute for Physiology, Saarland University, Homburg, GermanyInstitute for Physiology, Saarland University, Homburg, GermanyInstitute for Physiology, Saarland University, Homburg, GermanyInstitute for Physiology, Saarland University, Homburg, GermanyZentrum für Human- und Molekularbiologie, Saarland University, Homburg, GermanyGroup Nanoscale Cell Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, GermanyComputational Biology, Department of Biology, Friedrich-Alexander University, Erlangen, GermanyGroup Nanoscale Cell Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, GermanyZentrum für Human- und Molekularbiologie, Saarland University, Homburg, GermanyInstitute for Physiology, Saarland University, Homburg, GermanyVesicle 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 Ca2+-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.https://elifesciences.org/articles/17571neurotransmitter releaseexocytosissynaptobrevinmembrane fusion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Madhurima Dhara Antonio Yarzagaray Mazen Makke Barbara Schindeldecker Yvonne Schwarz Ahmed Shaaban Satyan Sharma Rainer A Böckmann Manfred Lindau Ralf Mohrmann Dieter Bruns |
spellingShingle |
Madhurima Dhara Antonio Yarzagaray Mazen Makke Barbara Schindeldecker Yvonne Schwarz Ahmed Shaaban Satyan Sharma Rainer A Böckmann Manfred Lindau Ralf Mohrmann Dieter Bruns v-SNARE transmembrane domains function as catalysts for vesicle fusion eLife neurotransmitter release exocytosis synaptobrevin membrane fusion |
author_facet |
Madhurima Dhara Antonio Yarzagaray Mazen Makke Barbara Schindeldecker Yvonne Schwarz Ahmed Shaaban Satyan Sharma Rainer A Böckmann Manfred Lindau Ralf Mohrmann Dieter Bruns |
author_sort |
Madhurima Dhara |
title |
v-SNARE transmembrane domains function as catalysts for vesicle fusion |
title_short |
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_sort |
v-snare transmembrane domains function as catalysts for vesicle fusion |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2016-06-01 |
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 Ca2+-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. |
topic |
neurotransmitter release exocytosis synaptobrevin membrane fusion |
url |
https://elifesciences.org/articles/17571 |
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