| First Author | Courtney NA | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 4076 |
| PubMed ID | 31501440 | Mgi Jnum | J:279393 |
| Mgi Id | MGI:6362406 | Doi | 10.1038/s41467-019-12015-w |
| Citation | Courtney NA, et al. (2019) Synaptotagmin 1 clamps synaptic vesicle fusion in mammalian neurons independent of complexin. Nat Commun 10(1):4076 |
| abstractText | Synaptic vesicle (SV) exocytosis is mediated by SNARE proteins. Reconstituted SNAREs are constitutively active, so a major focus has been to identify fusion clamps that regulate their activity in synapses: the primary candidates are synaptotagmin (syt) 1 and complexin I/II. Syt1 is a Ca(2+) sensor for SV release that binds Ca(2+) via tandem C2-domains, C2A and C2B. Here, we first determined whether these C2-domains execute distinct functions. Remarkably, the C2B domain profoundly clamped all forms of SV fusion, despite synchronizing residual evoked release and rescuing the readily-releasable pool. Release was strongly enhanced by an adjacent C2A domain, and by the concurrent binding of complexin to trans-SNARE complexes. Knockdown of complexin had no impact on C2B-mediated clamping of fusion. We postulate that the C2B domain of syt1, independent of complexin, is the molecular clamp that arrests SVs prior to Ca(2+)-triggered fusion. |
