title: Munc18-1 promotes large dense-core vesicle docking.
abstract: Secretory vesicles dock at the plasma membrane before Ca(2+) triggers their exocytosis. Exocytosis requires the assembly of SNARE complexes formed by the vesicle protein Synaptobrevin and the membrane proteins Syntaxin-1 and SNAP-25. We analyzed the role of Munc18-1, a cytosolic binding partner of Syntaxin-1, in large dense-core vesicle (LDCV) secretion. Calcium-dependent LDCV exocytosis was reduced 10-fold in mouse chromaffin cells lacking Munc18-1, but the kinetic properties of the remaining release, including single fusion events, were not different from controls. Concomitantly, mutant cells displayed a 10-fold reduction in morphologically docked LDCVs. Moreover, acute overexpression of Munc18-1 in bovine chromaffin cells increased the amount of releasable vesicles and accelerated vesicle supply. We conclude that Munc18-1 functions upstream of SNARE complex formation and promotes LDCV docking.
authors.affiliation: Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany. thomas.voets@med.kuleven.ac.be
authors.forename: T
authors.initials: T
authors.lastname: Voets
authors.forename: R F
authors.initials: RF
authors.lastname: Toonen
authors.forename: E C
authors.initials: EC
authors.lastname: Brian
authors.forename: H
authors.initials: H
authors.lastname: de Wit
authors.forename: T
authors.initials: T
authors.lastname: Moser
authors.forename: J
authors.initials: J
authors.lastname: Rettig
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: E
authors.initials: E
authors.lastname: Neher
authors.forename: M
authors.initials: M
authors.lastname: Verhage
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis / Q000502:physiology; D005260:Female; D005333:Fetus / Q000166:cytology; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D013572:Synaptic Vesicles / Q000378:metabolism*; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
chemical_list: D000954:Antigens, Surface; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; C494214:Stx1a protein, mouse; C497938:Stxbp1 protein, mouse; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins