Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones.

ABSTRACT: Active zones consist of protein scaffolds that are tightly attached to the presynaptic plasma membrane. They dock and prime synaptic vesicles, couple them to voltage-gated Ca²⁺ channels, and direct neurotransmitter release toward postsynaptic receptor domains. Simultaneous RIM + ELKS ablation disrupts these scaffolds, abolishes vesicle docking, and removes active zone-targeted Munc13, but some vesicles remain releasable. To assess whether this enduring vesicular fusogenicity is mediated by non-active zone-anchored Munc13 or is Munc13-independent, we ablated Munc13-1 and Munc13-2 in addition to RIM + ELKS in mouse hippocampal neurons. The hextuple knockout synapses lacked docked vesicles, but other ultrastructural features were near-normal despite the strong genetic manipulation.

SUBMITTER: Tan C 

PROVIDER: S-EPMC9822248 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature