ArticleBiophysical journal2015
High cholesterol obviates a prolonged hemifusion intermediate in fast SNARE-mediated membrane fusion.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Functionally distinct SNARE motifs of SNAP25 cooperate in SNARE assembly and membrane fusion.Biophysical journal · 2025Article
- Mechanistic Insights into Synaptotagmin-1 Mediated Membrane Fusion and Interactions.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Cholesterol imbalance and neurotransmission defects in neurodegeneration.Experimental & molecular medicine · 2024Review
- Mechanisms of SNARE proteins in membrane fusion.Nature reviews. Molecular cell biology · 2024Review
- Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer.Nature methods · 2023Article
- Requirement of Cholesterol for Calcium-Dependent Vesicle Fusion by Strengthening Synaptotagmin-1-Induced Membrane Bending.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Breaking free: endocytosis and endosomal escape of extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2023Review
- Review
- Role of the endoplasmic reticulum in synaptic transmission.Current opinion in neurobiology · 2022Review
- Review
- Drunken lipid membranes, not drunken SNARE proteins, promote fusion in a model of neurotransmitter release.Frontiers in molecular neuroscience · 2022Article
- Single-virus content-mixing assay reveals cholesterol-enhanced influenza membrane fusion efficiency.Biophysical journal · 2021Article
- Cholesterol stabilizes recombinant exocytic fusion pores by altering membrane bending rigidity.Biophysical journal · 2021Article
- In vitro single vesicle fusion assays based on pore-spanning membranes: merits and drawbacks.European biophysics journal : EBJ · 2021Review
- Ebola virus glycoprotein interacts with cholesterol to enhance membrane fusion and cell entry.Nature structural & molecular biology · 2021Article
- Fusion Pore Formation Observed during SNARE-Mediated Vesicle Fusion with Pore-Spanning Membranes.Biophysical journal · 2020Article
- Barcoding Biological Reactions with DNA-Functionalized Vesicles.Angewandte Chemie (International ed. in English) · 2019Review
- In vitro fusion of single synaptic and dense core vesicles reproduces key physiological properties.Nature communications · 2019Article
- Cholesterol and the Safety Factor for Neuromuscular Transmission.International journal of molecular sciences · 2019Review
- SNARE-Mediated Fusion of Single Chromaffin Granules with Pore-Spanning Membranes.Biophysical journal · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cholesterol is essential for exocytosis in secretory cells, but the exact molecular mechanism by which it facilitates exocytosis is largely unknown. Distinguishing contributions from the lateral organization and dynamics of membrane proteins to vesicle docking and fusion and the promotion of fusion pores by negative intrinsic spontaneous curvature and other mechanical effects of cholesterol have been elusive. To shed more light on this process, we examined the effect of cholesterol on SNARE-mediated membrane fusion in a single-vesicle assay that is capable of resolving docking and elementary steps of fusion with millisecond time resolution. The effect of cholesterol on fusion pore formation between synaptobrevin-2 (VAMP-2)-containing proteoliposomes and acceptor t-SNARE complex-containing planar supported bilayers was examined using both membrane and content fluorescent markers. This approach revealed that increasing cholesterol in either the t-SNARE or the v-SNARE membrane favors a mechanism of direct fusion pore opening, whereas low cholesterol favors a mechanism leading to a long-lived (>5 s) hemifusion state. The amount of cholesterol in the target membrane had no significant effect on docking of synaptobrevin vesicles. Comparative studies with α-tocopherol (vitamin E) show that the negative intrinsic spontaneous curvature of cholesterol and its presumed promotion of a very short-lived (<50 ms) lipid stalk intermediate is the main factor that favors rapid fusion pore opening at high cholesterol. This study also shows that this single-vesicle fusion assay can distinguish between hemifusion and full fusion with only a single lipid dye, thereby freeing up a fluorescence channel for the simultaneous measurement of another parameter in fast time-resolved fusion assays.
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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.