@article{4ff60600bab311df825b000ea68e967b,
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.",
author = "Weber, {Jens P} and Kerstin Reim and S{\o}rensen, {Jakob B}",
note = "Keywords: Amino Acid Sequence; Animals; Cells, Cultured; Gene Deletion; Hippocampus; Mice; Mice, Knockout; Molecular Sequence Data; Mutation; Sequence Alignment; Synaptic Transmission; Synaptosomal-Associated Protein 25",
year = "2010",
doi = "10.1038/emboj.2010.130",
language = "English",
volume = "29",
pages = "2477--90",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "15",
}