@article{11bd7a00fb7111de825d000ea68e967b,
title = "Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes",
abstract = "Munc18-1, a protein essential for regulated exocytosis in neurons and neuroendocrine cells, belongs to the family of Sec1/Munc18-like (SM) proteins. In vitro, Munc18-1 forms a tight complex with the SNARE syntaxin 1, in which syntaxin is stabilized in a closed conformation. Since closed syntaxin is unable to interact with its partner SNAREs SNAP-25 and synaptobrevin as required for membrane fusion, it has hitherto not been possible to reconcile binding of Munc18-1 to syntaxin 1 with its biological function. We now show that in intact and exocytosis-competent lawns of plasma membrane, Munc18-1 forms a complex with syntaxin that allows formation of SNARE complexes. Munc18-1 associated with membrane-bound syntaxin 1 can be effectively displaced by adding recombinant synaptobrevin but not syntaxin 1 or SNAP-25. Displacement requires the presence of endogenous SNAP-25 since no displacement is observed when chromaffin cell membranes from SNAP-25-deficient mice are used. We conclude that Munc18-1 allows for the formation of a complex between syntaxin and SNAP-25 that serves as an acceptor for vesicle-bound synaptobrevin and that thus represents an intermediate in the pathway towards exocytosis.",
author = "Zilly, {Felipe E} and S{\o}rensen, {Jakob B} and Reinhard Jahn and Thorsten Lang",
note = "Keywords: Animals; Binding Sites; Cell Membrane; Microscopy, Fluorescence; Models, Biological; Munc18 Proteins; PC12 Cells; Plasmids; Protein Binding; Qa-SNARE Proteins; R-SNARE Proteins; Rats; Recombinant Proteins; SNARE Proteins; Vesicle-Associated Membrane Protein 2",
year = "2006",
doi = "10.1371/journal.pbio.0040330",
language = "English",
volume = "4",
pages = "e330",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "10",
}