A Hyperactive Form of unc-13 Enhances Ca²⁺ Sensitivity and Synaptic Vesicle Release Probability in C. elegans.

ABSTRACT: Munc13 proteins play several roles in regulating short-term synaptic plasticity. However, the underlying molecular mechanisms remain largely unclear. Here we report that C. elegans UNC-13L, a Munc13-1 ortholog, has three domains that inhibit synaptic vesicle (SV) exocytosis. These include the X (sequence between C2A and C1), C1, and C2B domains. Deleting all three inhibitory domains produces a hyperactive UNC-13 (sUNC-13) that exhibits dramatically increased neurotransmitter release, Ca²⁺ sensitivity of release, and release probability. The vesicular pool in unc-13 mutants rescued by sUNC-13 exhibits a faster synaptic recovery and replenishment rate, demonstrating an important role of sUNC-13 in regulating synaptic plasticity. Analysis of double mutants suggests that sUNC-13 enh

SUBMITTER: Li L 

PROVIDER: S-EPMC6779330 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature