Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery.

ABSTRACT: Here, we introduce the full functional reconstitution of genetically validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, and Complexin) for synaptic vesicle priming and release in a geometry that enables detailed characterization of the fate of docked vesicles both before and after release is triggered with Ca²⁺. Using this setup, we identify new roles for diacylglycerol (DAG) in regulating vesicle priming and Ca²⁺-triggered release involving the SNARE assembly chaperone Munc13. We find that low concentrations of DAG profoundly accelerate the rate of Ca²⁺-dependent release, and high concentrations reduce clamping and permit extensive spontaneous release. As expected, DAG also increases the number of docked, release-ready vesicles. Dynam

SUBMITTER: Kalyana Sundaram RV 

PROVIDER: S-EPMC10450444 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature