ArticleNature communications2019
Munc18-1 is crucial to overcome the inhibition of synaptic vesicle fusion by αSNAP.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Eyedrop Administration of DPP-4 Inhibitors: A New Strategy for Treating Early Stages of Diabetic Retinal Disease.International journal of molecular sciences · 2026Review
- A PIP2-stabilized syntaxin-1a structure mapped with transition metal ion FRET and unnatural fluorescent amino acids at the plasma membrane.Structure (London, England : 1993) · 2026Article
- Recent Structural Insights into the Molecular Architecture of Synapses.Advances in neurobiology · 2026Review
- Syntaxin 3B Mediates Light-Dependent Interactions with STXBP1 and Arrestin 4: Distinct Roles in Rods and Cones.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Abnormal Transcytosis Mechanisms in the Pathogenesis of Hydrocephalus: A Review.International journal of molecular sciences · 2025Review
- The E3 Ubiquitin Ligase PRAJA1: A Key Regulator of Synaptic Dynamics and Memory Processes with Implications for Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Complexin regulation of synaptic vesicle release: mechanisms in the central nervous system and specialized retinal ribbon synapses.Cell communication and signaling : CCS · 2024Review
- 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
- Control of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region.Journal of molecular biology · 2024Article
- A practical guide for fast implementation of SNARE-mediated liposome fusion.Biophysics reports · 2024Article
- Control of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region.bioRxiv : the preprint server for biology · 2024Article
- The role of syntaxins in retinal function and health.Frontiers in cellular neuroscience · 2024Review
- Review
- Double mutation of open syntaxin and UNC-18 P334A leads to excitatory-inhibitory imbalance and impairs multiple aspects ofbioRxiv : the preprint server for biology · 2023Article
- Functional Roles of UNC-13/Munc13 and UNC-18/Munc18 in Neurotransmission.Advances in neurobiology · 2023Review
- Transcriptomic Analysis Reveals That Retinal Neuromodulation Is a Relevant Mechanism in the Neuroprotective Effect of Sitagliptin in an Experimental Model of Diabetic Retinopathy.International journal of molecular sciences · 2022Article
- A dynamic template complex mediates Munc18-chaperoned SNARE assembly.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Munc18-1 and Munc13-1 orchestrate assembly of the SNARE complex formed by syntaxin-1, SNAP-25 and synaptobrevin, allowing exquisite regulation of neurotransmitter release. Non-regulated neurotransmitter release might be prevented by αSNAP, which inhibits exocytosis and SNARE-dependent liposome fusion. However, distinct mechanisms of inhibition by αSNAP were suggested, and it is unknown how such inhibition is overcome. Using liposome fusion assays, FRET and NMR spectroscopy, here we provide a comprehensive view of the mechanisms underlying the inhibitory functions of αSNAP, showing that αSNAP potently inhibits liposome fusion by: binding to syntaxin-1, hindering Munc18-1 binding; binding to syntaxin-1-SNAP-25 heterodimers, precluding SNARE complex formation; and binding to trans-SNARE complexes, preventing fusion. Importantly, inhibition by αSNAP is avoided only when Munc18-1 binds first to syntaxin-1, leading to Munc18-1-Munc13-1-dependent liposome fusion. We propose that at least some of the inhibitory activities of αSNAP ensure that neurotransmitter release occurs through the highly-regulated Munc18-1-Munc13-1 pathway at the active zone.
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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.