SNARE-mediated membrane fusion arrests at pore expansion to regulate the volume of an organelle.

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Serval ID
serval:BIB_5A00C7C05A19
Type
Article: article from journal or magazin.
Collection
Publications
Title
SNARE-mediated membrane fusion arrests at pore expansion to regulate the volume of an organelle.
Journal
The EMBO journal
Author(s)
D'Agostino M., Risselada H.J., Endter L.J., Comte-Miserez V., Mayer A.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Publication state
Published
Issued date
01/10/2018
Peer-reviewed
Oui
Volume
37
Number
19
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Constitutive membrane fusion within eukaryotic cells is thought to be controlled at its initial steps, membrane tethering and SNARE complex assembly, and to rapidly proceed from there to full fusion. Although theory predicts that fusion pore expansion faces a major energy barrier and might hence be a rate-limiting and regulated step, corresponding states with non-expanding pores are difficult to assay and have remained elusive. Here, we show that vacuoles in living yeast are connected by a metastable, non-expanding, nanoscopic fusion pore. This is their default state, from which full fusion is regulated. Molecular dynamics simulations suggest that SNAREs and the SM protein-containing HOPS complex stabilize this pore against re-closure. Expansion of the nanoscopic pore to full fusion can thus be triggered by osmotic pressure gradients, providing a simple mechanism to rapidly adapt organelle volume to increases in its content. Metastable, nanoscopic fusion pores are then not only a transient intermediate but can be a long-lived, physiologically relevant and regulated state of SNARE-dependent membrane fusion.
Keywords
Membrane Fusion, Molecular Dynamics Simulation, SNARE Proteins/chemistry, SNARE Proteins/genetics, SNARE Proteins/metabolism, Saccharomyces cerevisiae/chemistry, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/chemistry, Saccharomyces cerevisiae Proteins/genetics, Saccharomyces cerevisiae Proteins/metabolism, Vacuoles/chemistry, Vacuoles/genetics, Vacuoles/metabolism, SNAREs, endosomes, lysosomes, membrane fusion, vacuoles
Pubmed
Web of science
Open Access
Yes
Create date
29/08/2018 15:48
Last modification date
03/10/2019 6:09
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