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Opposing functions of two sub‐domains of the SNARE‐complex in neurotransmission
Author(s) -
Weber Jens P,
Reim Kerstin,
Sørensen Jakob B
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.130
Subject(s) - exocytosis , neurosecretion , biology , neuroscience , biochemistry , secretion
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.