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PMID: 16365164 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transition from hemifusion to pore opening is rate limiting for vacuole membrane fusion.

The Journal of cell biology ·Vol. 171 ·No. 6 ·2005-12-19 ·Pages 981-90

Reese C, Mayer A

Abstract

Fusion pore opening and expansion are considered the most energy-demanding steps in viral fusion. Whether this also applies to soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE)- and Rab-dependent fusion events has been unknown. We have addressed the problem by characterizing the effects of lysophosphatidylcholine (LPC) and other late-stage inhibitors on lipid mixing and pore opening during vacuole fusion. LPC inhibits fusion by inducing positive curvature in the bilayer and changing its biophysical properties. The LPC block reversibly prevented formation of the hemifusion intermediate that allows lipid, but not content, mixing. Transition from hemifusion to pore opening was sensitive to guanosine-5'-(gamma-thio)triphosphate. It required the vacuolar adenosine triphosphatase V0 sector and coincided with its transformation. Pore opening was rate limiting for the reaction. As with viral fusion, opening the fusion pore may be the most energy-demanding step for intracellular, SNARE-dependent fusion reactions, suggesting that fundamental aspects of lipid mixing and pore opening are related for both systems.

MeSH Terms
Biomarkers Kinetics Lipid Bilayers/chemistry Lysophosphatidylcholines/metabolism,pharmacology Membrane Fusion/drug effects,physiology Models, Biological Nuclear Pore/physiology SNARE Proteins/metabolism Saccharomyces cerevisiae/physiology Time Factors Vacuoles/drug effects,physiology
Chemicals
Biomarkers Lipid Bilayers Lysophosphatidylcholines SNARE Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Reese Christoph
Département de Biochimie, Université de Lausanne, 1066 Epalinges, Switzerland.
Mayer Andreas
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200510018
Published
2005-12-19
Pages
981-90
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171322
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200510018 PMC Full Text View journal details
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