title: Vesicle fusion probability is determined by the specific interactions of munc18.
abstract: Mammalian-regulated secretion is absolutely dependent on four evolutionarily conserved proteins: three SNARE proteins and munc18. Dissecting the functional outcomes of the spatially organized protein interactions between these factors has been difficult because of the close interrelationship between different binding modes. Here, we investigated the spatial distribution of single munc18 molecules at the plasma membrane of cells and the underlying interactions between syntaxin and munc18. Disruption of munc18 binding to the N-terminal peptide motif of syntaxin did not alter munc18 localization on the plasma membrane but had a pronounced influence on the behavior of secretory vesicles and their likelihood to undergo fusion. We therefore conclude that interaction with the syntaxin N-peptide can confer differential release probabilities to secretory vesicles and may contribute to the delineation of secretory vesicle pools.
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Annya M
authors.initials: AM
authors.lastname: Smyth
authors.forename: Colin
authors.initials: C
authors.lastname: Rickman
authors.forename: Rory R
authors.initials: RR
authors.lastname: Duncan
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology*; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism*
chemical_list: D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins
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