Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release.

ABSTRACT: Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca²⁺ release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca²⁺ 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 tr

SUBMITTER: Tagliatti E 

PROVIDER: S-EPMC7035618 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature