Munc13-1 couples DAG and Ca²⁺ signaling to dynamic vesicle priming, synaptic short-term plasticity, and posttetanic potentiation.

ABSTRACT: Synaptic strength and plasticity are fine-tuned by neuromodulation and use-dependent second-messenger signaling. Presynaptic diacylglycerol (DAG), Ca²⁺, and Ca²⁺-calmodulin signaling converge on the essential synaptic vesicle (SV) priming protein Munc13-1 via its regulatory C₁, C₂B, and CaM-binding domains. Using brainstem-specific heterozygous mice expressing a DAG-binding-deficient Munc13-1 variant (Munc13-1^H567K), we compared synaptic transmission in situ at glutamatergic calyx of Held synapses carrying either a single Munc13-1^H567K or a single Munc13-1^wt allele. Munc13-1^H567K/- synapses show enhanced initial strength but impaired steady-state release and slower recovery from depression. These defici

SUBMITTER: Ranjan M 

PROVIDER: S-EPMC12904202 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature