| First Author | Weber JP | Year | 2010 |
| Journal | EMBO J | Volume | 29 |
| Issue | 15 | Pages | 2477-90 |
| PubMed ID | 20562829 | Mgi Jnum | J:163403 |
| Mgi Id | MGI:4821899 | Doi | 10.1038/emboj.2010.130 |
| Citation | Weber JP, et al. (2010) Opposing functions of two sub-domains of the SNARE-complex in neurotransmission. EMBO J 29(15):2477-90 |
| abstractText | 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. |
