title: Opposing functions of two sub-domains of the SNARE-complex in neurotransmission.
abstract: The SNARE-complex consisting of synaptobrevin-2/VAMP-2, SNAP-25 and syntaxin-1 is essential for evoked neurotransmission and also involved in spontaneous release. Here, we used cultured autaptic hippocampal neurons from Snap-25 null mice rescued with mutants challenging the C-terminal, N-terminal and middle domains of the SNARE-bundle to dissect out the involvement of these domains in neurotransmission. We report that the stabilities of two different sub-domains of the SNARE-bundle have opposing functions in setting the probability for both spontaneous and evoked neurotransmission. Destabilizing the C-terminal end of the SNARE-bundle abolishes spontaneous neurotransmitter release and reduces evoked release probability, indicating that the C-terminal end promotes both modes of release. In contrast, destabilizing the middle or deleting the N-terminal end of the SNARE-bundle increases both spontaneous and evoked release probabilities. In both cases, spontaneous release was affected more than evoked neurotransmission. In addition, the N-terminal deletion delays vesicle priming after a high-frequency train. We propose that the stability of N-terminal two-thirds of the SNARE-bundle has a function for vesicle priming and limiting spontaneous release.
authors.affiliation: Molecular Mechanisms of Exocytosis, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Weber
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reim
authors.forename: Jakob B
authors.initials: JB
authors.lastname: Sørensen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D017353:Gene Deletion; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D009435:Synaptic Transmission; D050825:Synaptosomal-Associated Protein 25 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25