ArticleBiochemistry2011
Molecular mechanism of cholesterol- and polyphosphoinositide-mediated syntaxin clustering.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- 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
- Integrating AlphaFold2, RoseTTAFold2, and HADDOCK to refine Protein-Protein Interaction (PPI) candidate selection: A case study with ZWINT.Biochemistry and biophysics reports · 2026Article
- The lipid flippase MoNeo1 mediates vesicle trafficking and pathogenicity in Magnaporthe oryzae.Stress biology · 2026Article
- Munc18 modulates syntaxin phase separation to promote exocytosis.Nature neuroscience · 2026Article
- PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Syntaxin clusters and cholesterol affect the mobility of Syntaxin1a.Biophysical journal · 2025Article
- Functionally distinct SNARE motifs of SNAP25 cooperate in SNARE assembly and membrane fusion.Biophysical journal · 2025Article
- Lipid and Lipidation in Membrane Fusion.The Journal of membrane biology · 2022Review
- Article
- Munc18-dependent and -independent clustering of syntaxin in the plasma membrane of cultured endocrine cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cholesterol stabilizes recombinant exocytic fusion pores by altering membrane bending rigidity.Biophysical journal · 2021Article
- Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021Review
- The Effects of Regulatory Lipids on Intracellular Membrane Fusion Mediated by Dynamin-Like GTPases.Frontiers in cell and developmental biology · 2020Review
- Cholesterol and the Safety Factor for Neuromuscular Transmission.International journal of molecular sciences · 2019Review
- Lipid⁻Protein Interactions in Niemann⁻Pick Type C Disease: Insights from Molecular Modeling.International journal of molecular sciences · 2019Article
- Oligomerisation of Synaptobrevin-2 Studied by Native Mass Spectrometry and Chemical Cross-Linking.Journal of the American Society for Mass Spectrometry · 2019Article
- Mechanism of membrane fusion: protein-protein interaction and beyond.International journal of physiology, pathophysiology and pharmacology · 2019Review
- Syntaxin clusters at secretory granules in a munc18-bound conformation.Molecular biology of the cell · 2018Article
- The Dual Function of the Polybasic Juxtamembrane Region of Syntaxin 1A in Clamping Spontaneous Release and Stimulating CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- t-SNARE Transmembrane Domain Clustering Modulates Lipid Organization and Membrane Curvature.Journal of the American Chemical Society · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The neuronal acceptor SNARE complex that functions as the receptor for synaptic vesicle docking and fusion at the presynaptic membrane is composed of the single-span transmembrane protein syntaxin-1A and the palmitoylated soluble protein SNAP-25. Previously, we explored interactions that promote the formation of syntaxin-1A clusters in membranes. Cholesterol activates clustering in native and model membranes, and its depletion in neuroendocrine cells results in a homogeneous distribution of the protein. However, as little as 1 mol % phosphatidylinositol 4,5-bisphosphate (PI-4,5-P(2)) or 20 mol % phosphatidylserine was found to disperse syntaxin-1A clusters [Murray, D. H., and Tamm, L. K. (2009) Biochemistry 48, 4617-4625]. Strong evidence suggests that syntaxin-1A and its synaptic vesicle cognate synaptobrevin both interact directly with PI-4,5-P(2) and that this interaction activates fusion. However, the molecular details of this interaction and its relationship to the partial dispersion of syntaxin-1A clusters remain largely unexplored. Hence, we mutated the polybasic juxtamembrane motif of syntaxin-1A and found several residues that partially or fully abrogate the electrostatic interaction with PI-4,5-P(2). We further show that even in the presence of physiological concentrations of phosphatidylserine, the PI-4,5-P(2)-syntaxin interaction is sufficiently strong to disrupt syntaxin-1A clustering. The stereochemistry of PI-4,5-P(2) is not critical for this interaction as other polyphosphoinositides have similar effects. Forming an acceptor SNARE complex between syntaxin-1A and SNAP-25 weakens but does not abrogate cholesterol/PI-4,5-P(2)-controlled cluster formation. Potential consequences of these interactions with respect to synaptic vesicle fusion are discussed.
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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.