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TitleTwo successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 7222, Year 2025
Publish dateAug 5, 2025
AuthorsManindra Bera / Kirill Grushin / R Venkat Kalyana Sundaram / Jasmine S Hinzen / Joyce Chen / Atrouli Chatterjee / Abhijith Radhakrishnan / Seong Lee / Murugesh Padmanarayana / Jeff Coleman / Frédéric Pincet / James E Rothman / Jeremy S Dittman /
PubMed AbstractThe critical protein Munc13 serves numerous roles in the docking and priming of synaptic vesicles. On the presynaptic plasma membrane, Munc13 is organized into nanoclusters corresponding to release ...The critical protein Munc13 serves numerous roles in the docking and priming of synaptic vesicles. On the presynaptic plasma membrane, Munc13 is organized into nanoclusters corresponding to release sites where synaptic vesicles dock and fuse. However, it is currently not known whether there is any organization of Munc13 monomers within the nanoclusters. Recent work suggests that Munc13 may spontaneously self-organize into homo-oligomers, raising the possibility that synaptic nanoclusters comprise organized assemblies of Munc13. Here we investigate the functional impact of two distinct Munc13 core domain oligomers comprising C1-C2B-MUN-C2C both in vitro and in vivo. Interface mutations that specifically destabilized oligomeric assemblies of Munc13 disrupted vesicle docking, trans-SNARE formation, and Ca-triggered vesicle fusion in vitro and impaired neurotransmitter secretion and motor nervous system function in vivo. We suggest that a sequence of oligomeric Munc13 complexes rapidly couple vesicle docking to vesicle priming via the assembly of a precise number of SNAREs.
External linksNat Commun / PubMed:40764329 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution36.0 Å
Structure data

EMDB-71039: Subtomogram average of Munc13-1 C1-C2B-MUN-C2C F1176N/I1215N mutant 2D crystal between lipid bilayers
Method: EM (subtomogram averaging) / Resolution: 36.0 Å

Source
  • Rattus norvegicus (Norway rat)

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