ArticleThe Journal of biological chemistry2014
An extended helical conformation in domain 3a of Munc18-1 provides a template for SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex assembly.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 132 citations in OpenAlex.
- STXBP1 Variants Associated With Epilepsy With Variable Severity.CNS neuroscience & therapeutics · 2026Article
- Munc18 binds to and organizes membrane-bound acceptor Q-SNARE complexes in a fashion that depends on the membrane's lipid composition.bioRxiv : the preprint server for biology · 2026Article
- Munc18-1 is crucial for photoreceptor function, survival and regulation of syntaxin-3 localization and expression.Scientific reports · 2026Article
- 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
- Recent Structural Insights into the Molecular Architecture of Synapses.Advances in neurobiology · 2026Review
- Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.FEBS open bio · 2025Article
- A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- After their membrane assembly, Sec18 (NSF) and Sec17 (SNAP) promote membrane fusion.Molecular biology of the cell · 2024Article
- Intermediate steps in the formation of neuronal SNARE complexes.The Journal of biological chemistry · 2024Article
- Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Review
- A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release.bioRxiv : the preprint server for biology · 2024Article
- Disease-linked mutations in Munc18-1 deplete synaptic Doc2.Brain : a journal of neurology · 2024Article
- SM protein Sly1 and a SNARE Habc domain promote membrane fusion through multiple mechanisms.The Journal of cell biology · 2024Article
- Beyond the MUN domain, Munc13 controls priming and depriming of synaptic vesicles.Cell reports · 2024Article
- Reduced synaptic depression in human neurons carrying homozygous disease-causing STXBP1 variant L446F.Human molecular genetics · 2024Article
- Sec18 binds the tethering/SM complex HOPS to engage the Qc-SNARE for membrane fusion.Molecular biology of the cell · 2024Article
- Molecular mechanism underlying SNARE-mediated membrane fusion enlightened by all-atom molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Control of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region.Journal of molecular biology · 2024Article
- Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes.Nature communications · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Munc18-1, a SEC1/Munc18 protein and key regulatory protein in synaptic transmission, can either promote or inhibit SNARE complex assembly. Although the binary inhibitory interaction between Munc18-1 and closed syntaxin 1 is well described, the mechanism of how Munc18-1 stimulates membrane fusion remains elusive. Using a reconstituted assay that resolves vesicle docking, priming, clamping, and fusion during synaptic exocytosis, we show that helix 12 in domain 3a of Munc18-1 stimulates SNAREpin assembly and membrane fusion. A single point mutation (L348R) within helix 12 selectively abolishes VAMP2 binding and the stimulatory function of Munc18-1 in membrane fusion. In contrast, targeting a natural switch site (P335A) at the start of helix 12, which can result in an extended α-helical conformation, further accelerates lipid-mixing. Together with structural modeling, the data suggest that helix 12 provides a folding template for VAMP2, accelerating SNAREpin assembly and membrane fusion. Analogous SEC1/Munc18-SNARE interactions at other transport steps may provide a general mechanism to drive lipid bilayer merger. At the neuronal synapse, Munc18-1 may convert docked synaptic vesicles into a readily releasable pool.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.