Journal
EMBO JOURNAL
Volume 29, Issue 15, Pages 2477-2490Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.130
Keywords
exocytosis; SNAP-25; SNARE-complex; spontaneous neurotransmitter release; synaptic transmission
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Funding
- Deutsche Forschungsgemeinschaft [GRK-521]
- Lundbeck Foundation
- Danish Medical Research council
- Gottingen Graduate School for Neurosciences and Molecular Biosciences (GGNB)
- [Graduiertenkolleg 521]
- Lundbeck Foundation [R28-2008-1976] Funding Source: researchfish
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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. The EMBO Journal (2010) 29, 2477-2490. doi:10.1038/emboj.2010.130; Published online 18 June 2010
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