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

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  • Chao Tan
  • Giovanni de Nola
  • Claire Qiao
  • Imig, Cordelia
  • Richard T Born
  • Nils Brose
  • Pascal S Kaeser
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 towards 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. Removing Munc13 in addition to RIM+ELKS impaired action potential-evoked vesicle fusion more strongly than RIM+ELKS knockout by further decreasing the releasable vesicle pool. Hence, Munc13 can support some fusogenicity without RIM and ELKS, and presynaptic recruitment of Munc13, even without active zone-anchoring, suffices to generate some fusion-competent vesicles
Original languageEnglish
Article number:e79077
JournaleLife
Volume11
Number of pages23
ISSN2050-084X
DOIs
Publication statusPublished - 2022

ID: 328300118