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

Authors
Journal
The Journal of Cell Biology
0021-9525
Publisher
The Rockefeller University Press
Publication Date
Volume
171
Issue
6
Identifiers
DOI: 10.1083/jcb.200510018
Keywords
  • Biological Markers
  • Kinetics
  • Lipid Bilayers/Chemistry
  • Lysophosphatidylcholines/Metabolism
  • Lysophosphatidylcholines/Pharmacology
  • Membrane Fusion/Drug Effects
  • Membrane Fusion/Physiology
  • Models
  • Biological
  • Nuclear Pore/Physiology
  • Snare Proteins/Metabolism
  • Saccharomyces Cerevisiae/Physiology
  • Time Factors
  • Vacuoles/Drug Effects
  • Vacuoles/Physiology
Disciplines
  • Biology
  • Physics

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.

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