ArticleNature neuroscience2026
Munc18 modulates syntaxin phase separation to promote exocytosis.
Article in Nature neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Lipid Disorder and PIP2-Regulated Clustering of Syntaxin-1 JMD-TMD Regions Govern Membrane Fusion Competence.International journal of molecular sciences · 2026Article
- Munc18 reprograms the intrinsic neuronal SNARE complex assembly pathway.bioRxiv : the preprint server for biology · 2026Article
- Structural remodeling of target-SNARE protein complexes by NSF enables synaptic transmission.Nature communications · 2025Article
- Structural remodeling of target-SNARE protein complexes by NSF enables synaptic transmission.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin mediates neuronal exocytosis and self-assembles into large clusters in the plasma membrane. The formation and function of these clusters, and whether they promote or inhibit synaptic-vesicle fusion, remain unclear. Here using optogenetic control of syntaxin clustering in vitro and in vivo, as a light-inducible gain-of-function assay, we show that light-enhanced clustering reduces both spontaneous and triggered vesicle fusion, and this impairs mouse hunting behavior. Cluster formation is induced by liquid-liquid phase separation (LLPS) of the SNARE domain of syntaxin. For the regulatory mechanism, Munc18, which is known to alter syntaxin conformation, acts to reduce LLPS for cluster formation, thereby promoting active syntaxin. These results suggest that exocytosis regulation involves LLPS-induced syntaxin clusters that serve as a syntaxin reservoir from which Munc18 captures syntaxin monomers to form a syntaxin-Munc18 complex, setting the stage for efficient fusion.
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Registered trials
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