Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30622273.
- Also identified by DOI 10.1038/s41467-018-08028-6 and PMC identifier 6325239.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The transition of the Munc18-1/syntaxin-1 complex to the SNARE complex, a key step involved in exocytosis, is regulated by Munc13-1, SNAP-25 and synaptobrevin-2, but the underlying mechanism remains elusive. Here, we identify an interaction between Munc13-1 and the membrane-proximal linker region of synaptobrevin-2, and reveal its essential role in transition and exocytosis. Upon this interaction, Munc13-1 not only recruits synaptobrevin-2-embedded vesicles to the target membrane but also renders the synaptobrevin-2 SNARE motif more accessible to the Munc18-1/syntaxin-1 complex. Afterward, the entry of SNAP-25 leads to a half-zippered SNARE assembly, which eventually dissociates the Munc18-1/syntaxin-1 complex to complete SNARE complex formation. Our data suggest that Munc18-1 and Munc13-1 together serve as a functional template to orchestrate SNARE complex assembly.
Medical subject headings
- Munc18 Proteins
- Nerve Tissue Proteins
- Synaptosomal-Associated Protein 25
- Syntaxin 1
- Vesicle-Associated Membrane Protein 2