| First Author | Tagliatti E | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 7 | Pages | 3819-3827 |
| PubMed ID | 32015138 | Mgi Jnum | J:285732 |
| Mgi Id | MGI:6393097 | Doi | 10.1073/pnas.1920403117 |
| Citation | Tagliatti E, et al. (2020) Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release. Proc Natl Acad Sci U S A 117(7):3819-3827 |
| abstractText | Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca(2+) release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca(2+) activation mechanism has been well-characterized, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerization provides the molecular basis for the Syt1 clamping function. This follows from the investigation of a designed mutation (F349A), which selectively destabilizes Syt1 oligomerization. Using a combination of fluorescence imaging and electrophysiology in neocortical synapses, we show that Syt1(F349A) is more efficient than wild-type Syt1 (Syt1(WT)) in triggering synchronous transmitter release but fails to clamp spontaneous and synaptotagmin 7 (Syt7)-mediated asynchronous release components both in rescue (Syt1(-/-) knockout background) and dominant-interference (Syt1(+/+) background) conditions. Thus, we conclude that Ca(2+)-sensitive Syt1 oligomers, acting as an exocytosis clamp, are critical for maintaining the balance among the different modes of neurotransmitter release. |
