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PMID: 27343350 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

v-SNARE transmembrane domains function as catalysts for vesicle fusion.

eLife ·Vol. 5 ·2016-00-25

Dhara M, Yarzagaray A, Makke M, Schindeldecker B, Schwarz Y, Shaaban A, Sharma S, Böckmann RA, Lindau M, Mohrmann R, Bruns D

Abstract

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.

Keywords
exocytosis membrane fusion mouse neuroscience neurotransmitter release synaptobrevin
MeSH Terms
Animals Cells, Cultured DNA Mutational Analysis Exocytosis Membrane Fusion Mice Models, Biological Mutant Proteins/chemistry,genetics,metabolism Protein Conformation Secretory Vesicles/metabolism Vesicle-Associated Membrane Protein 2/chemistry,genetics,metabolism
Chemicals
Mutant Proteins Vesicle-Associated Membrane Protein 2
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Dhara Madhurima
Institute for Physiology, Saarland University, Homburg, Germany.
Yarzagaray Antonio
Institute for Physiology, Saarland University, Homburg, Germany.
Makke Mazen
Institute for Physiology, Saarland University, Homburg, Germany.
Schindeldecker Barbara
Institute for Physiology, Saarland University, Homburg, Germany.
Schwarz Yvonne
Institute for Physiology, Saarland University, Homburg, Germany.
Shaaban Ahmed
Zentrum für Human- und Molekularbiologie, Saarland University, Homburg, Germany.
Sharma Satyan
Group Nanoscale Cell Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Böckmann Rainer A ORCID
Computational Biology, Department of Biology, Friedrich-Alexander University, Erlangen, Germany.
Lindau Manfred
Group Nanoscale Cell Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Mohrmann Ralf
Zentrum für Human- und Molekularbiologie, Saarland University, Homburg, Germany.
Bruns Dieter ORCID
Institute for Physiology, Saarland University, Homburg, Germany.
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Article Info
Journal
eLife
Abbr.
Elife
ISSN
2050-084X
DOI
10.7554/eLife.17571
Published
2016-00-25
Epub
2016-00-25
Language
English
Region
England
NLM ID
101579614
PMCID
PMC4972536
Subset
IM
Grants
NIGMS NIH HHS · R01 GM121787 · United States
External Links
PubMed source DOI: 10.7554/eLife.17571 PMC Full Text View journal details
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