Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release

Manindra 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 () and Jeremy S. Dittman ()
Additional contact information
Manindra Bera: Yale University
Kirill Grushin: Yale University
R. Venkat Kalyana Sundaram: Yale University
Jasmine S. Hinzen: Weill Cornell Medicine
Joyce Chen: Weill Cornell Medicine
Atrouli Chatterjee: Yale University
Abhijith Radhakrishnan: Yale University
Seong Lee: Yale University
Murugesh Padmanarayana: Weill Cornell Medicine
Jeff Coleman: Yale University
Frédéric Pincet: Yale University
James E. Rothman: Yale University
Jeremy S. Dittman: Weill Cornell Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract 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 Ca2+-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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62420-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62420-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62420-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().