Drunken lipid membranes, not drunken SNARE proteins, promote fusion in a model of neurotransmitter release.

Autor:	Coffman RE; Neuroscience Center, Brigham Young University, Provo, UT, United States., Kraichely KN; Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, United States., Kreutzberger AJB; Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, United States., Kiessling V; Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, United States., Tamm LK; Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, United States., Woodbury DJ; Neuroscience Center, Brigham Young University, Provo, UT, United States.; Department of Cell Biology and Physiology, Brigham Young University, Provo, UT, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2022 Oct 14; Vol. 15, pp. 1022756. Date of Electronic Publication: 2022 Oct 14 (Print Publication: 2022).
DOI:	10.3389/fnmol.2022.1022756
Abstrakt:	Alcohol affects many neuronal proteins that are upstream or down-stream of synaptic vesicle fusion and neurotransmitter release. Less well studied is alcohol's effect on the fusion machinery including SNARE proteins and lipid membranes. Using a SNARE-driven fusion assay we show that fusion probability is significantly increased at 0.4% v/v (68 mM) ethanol; but not with methanol up to 10%. Ethanol appears to act directly on membrane lipids since experiments focused on protein properties [circular dichroism spectrometry, site-directed fluorescence interference contrast (sdFLIC) microscopy, and vesicle docking results] showed no significant changes up to 5% ethanol, but a protein-free fusion assay also showed increased lipid membrane fusion rates with 0.4% ethanol. These data show that the effects of high physiological doses of ethanol on SNARE-driven fusion are mediated through ethanol's interaction with the lipid bilayer of membranes and not SNARE proteins, and that methanol affects lipid membranes and SNARE proteins only at high doses. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Coffman, Kraichely, Kreutzberger, Kiessling, Tamm and Woodbury.)
Databáze:	MEDLINE
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