title: Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission.
abstract: Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission.
authors.affiliation: Department of Functional Genomics and Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Meijer
authors.forename: Pawel
authors.initials: P
authors.lastname: Burkhardt
authors.forename: Heidi
authors.initials: H
authors.lastname: de Wit
authors.forename: Ruud F
authors.initials: RF
authors.lastname: Toonen
authors.forename: Dirk
authors.initials: D
authors.lastname: Fasshauer
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
mesh_terms: D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D051938:Munc18 Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D017354:Point Mutation; D011485:Protein Binding; D050600:SNARE Proteins / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles
chemical_list: D051938:Munc18 Proteins; D050600:SNARE Proteins