ArticleProtein science : a publication of the Protein Society2020
Re-examining how Munc13-1 facilitates opening of syntaxin-1.
Article in Protein science : a publication of the Protein Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Guiding AlphaFold to predict how Munc13-1 opens Syntaxin-1.FEBS open bio · 2026Article
- SNAP-25 disease variants affect synaptic transmission by destabilizing SNARE complexes within a multimeric SNARE ring.Cell reports · 2026Article
- Independently engaging protein tethers of different length enhance synaptic vesicle trafficking to the plasma membrane.The Journal of physiology · 2025Article
- RIM and MUNC13 membrane-binding domains are essential for neuropeptide secretion.The Journal of cell biology · 2025Article
- Exploring the structural dynamics of the vesicle priming machinery.Biochemical Society transactions · 2024Review
- Mechanisms of SNARE proteins in membrane fusion.Nature reviews. Molecular cell biology · 2024Review
- Review
- SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023Article
- Analysis of tripartite Synaptotagmin-1-SNARE-complexin-1 complexes in solution.FEBS open bio · 2023Article
- On the difficulties of characterizing weak protein interactions that are critical for neurotransmitter release.FEBS open bio · 2022Review
- Neuronal SNARE complex assembly guided by Munc18-1 and Munc13-1.FEBS open bio · 2022Review
- Energetics, kinetics, and pathways of SNARE assembly in membrane fusion.Critical reviews in biochemistry and molecular biology · 2022Review
- Article
- SNARE assembly enlightened by cryo-EM structures of a synaptobrevin-Munc18-1-syntaxin-1 complex.Science advances · 2022Article
- Molecular Mechanisms Underlying Neurotransmitter Release.Annual review of biophysics · 2022Review
- Control of neurotransmitter release by two distinct membrane-binding faces of the Munc13-1 CeLife · 2021Article
- Chaperoning SNARE Folding and Assembly.Annual review of biochemistry · 2021Review
- (M)Unc13s in Active Zone Diversity: AFrontiers in synaptic neuroscience · 2021Review
- Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association.Molecular syndromology · 2020Article
- CaeLife · 2020Article
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
Munc13-1 is crucial for neurotransmitter release and, together with Munc18-1, orchestrates assembly of the neuronal SNARE complex formed by syntaxin-1, SNAP-25, and synaptobrevin. Assembly starts with syntaxin-1 folded into a self-inhibited closed conformation that binds to Munc18-1. Munc13-1 is believed to catalyze the opening of syntaxin-1 to facilitate SNARE complex formation. However, different types of Munc13-1-syntaxin-1 interactions have been reported to underlie this activity, and the critical nature of Munc13-1 for release may arise because of its key role in bridging the vesicle and plasma membranes. To shed light into the mechanism of action of Munc13-1, we have used NMR spectroscopy, SNARE complex assembly experiments, and liposome fusion assays. We show that point mutations in a linker region of syntaxin-1 that forms intrinsic part of the closed conformation strongly impair stimulation of SNARE complex assembly and liposome fusion mediated by Munc13-1 fragments, even though binding of this linker region to Munc13-1 is barely detectable. Conversely, the syntaxin-1 SNARE motif clearly binds to Munc13-1, but a mutation that disrupts this interaction does not affect SNARE complex assembly or liposome fusion. We also show that Munc13-1 cannot be replaced by an artificial tethering factor to mediate liposome fusion. Overall, these results emphasize how very weak interactions can play fundamental roles in promoting conformational transitions and strongly support a model whereby the critical nature of Munc13-1 for neurotransmitter release arises not only from its ability to bridge two membranes but also from an active role in opening syntaxin-1 via interactions with the linker.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.