title: The functions of Munc18-1 in regulated exocytosis.
abstract: The activation of regulated exocytosis occurs by a rise in cytosolic Ca(2+) concentration. Synaptotagmins act as the Ca(2+) sensors, whereas the machinery that allows fusion of secretory vesicles with the plasma membrane consists of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, including syntaxin 1, SNAP-25, and VAMP. Within the pathway leading to exocytosis, there is an essential requirement for a member of the conserved Sec1/Munc18 (SM) protein family, which in neurotransmitter and neurohormone release in mammalian cells is Munc18-1. The exact role of Munc18-1 and the steps within exocytosis in which it acts have been intensively investigated. Current evidence suggests that Munc18-1 acts via distinct modes of interactions with syntaxin 1 and the other SNARE proteins and influences all of the steps leading to exocytosis, including vesicle recruitment, tethering, docking, priming, and membrane fusion.
authors.affiliation: The Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Liverpool, United Kingdom. burgoyne@liv.ac.uk
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burgoyne
authors.forename: Jeff W
authors.initials: JW
authors.lastname: Barclay
authors.forename: Leo F
authors.initials: LF
authors.lastname: Ciufo
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Graham
authors.forename: Mark T W
authors.initials: MT
authors.lastname: Handley
authors.forename: Alan
authors.initials: A
authors.lastname: Morgan
mesh_terms: D000818:Animals; D005089:Exocytosis; D006801:Humans; D051938:Munc18 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D050765:Qa-SNARE Proteins / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; D020692:rab3 GTP-Binding Proteins