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- Title
Opposing functions of two sub-domains of the SNARE-complex in neurotransmission.
- Authors
Weber, Jens P.; Reim, Kerstin; Sørensen, Jakob B.
- 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.
- Subjects
NEURAL transmission; NEURONS; NEUROTRANSMITTERS; MICE; NERVOUS system
- Publication
EMBO Journal, 2010, Vol 29, Issue 15, p2477
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/emboj.2010.130