ArticleProceedings of the National Academy of Sciences of the United States of America2011
In vitro system capable of differentiating fast Ca2+-triggered content mixing from lipid exchange for mechanistic studies of neurotransmitter release.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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116 citing papers in PubMed, 155 citations in OpenAlex.
- Molecular mechanism of cholesterol-dependent membrane fusion in SARS-CoV-2 entry.Signal transduction and targeted therapy · 2026Article
- Highly stable planar asymmetric suspended membranes for investigating protein dynamics and membrane fusion.Nature protocols · 2025Review
- Uncovering the Mechanisms of Intracellular Membrane Trafficking by Reconstituted Membrane Systems.Membranes · 2025Review
- Mechanistic Insights into Synaptotagmin-1 Mediated Membrane Fusion and Interactions.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Unveiling Interactions between Self-Assembling Peptides and Neuronal Membranes.Langmuir : the ACS journal of surfaces and colloids · 2024Article
- Invagination of Giant Unilamellar Vesicles upon Membrane Mixing with Native Vesicles.ACS omega · 2024Article
- Observing isolated synaptic vesicle association and fusion ex vivo.Nature protocols · 2024Review
- Beyond the MUN domain, Munc13 controls priming and depriming of synaptic vesicles.Cell reports · 2024Article
- Mechanisms of SNARE proteins in membrane fusion.Nature reviews. Molecular cell biology · 2024Review
- The Core Complex of the CaJournal of molecular biology · 2023Review
- Analysis of tripartite Synaptotagmin-1-SNARE-complexin-1 complexes in solution.FEBS open bio · 2023Article
- SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023Article
- On the difficulties of characterizing weak protein interactions that are critical for neurotransmitter release.FEBS open bio · 2022Review
- The beginning and the end of SNARE-induced membrane fusion.FEBS open bio · 2022Review
- Molecular Mechanisms Underlying Neurotransmitter Release.Annual review of biophysics · 2022Review
- Article
- Screening of Hydrocarbon-Stapled Peptides for Inhibition of Calcium-Triggered Exocytosis.Frontiers in pharmacology · 2022Article
- A theory of synaptic transmission.eLife · 2021Article
- Single-virus content-mixing assay reveals cholesterol-enhanced influenza membrane fusion efficiency.Biophysical journal · 2021Article
- Liposome fusion with orthogonal coiled coil peptides as fusogens: the efficacy of roleplaying peptides.Chemical science · 2021Article
56 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 1 country.
Funding
Abstract
Understanding the molecular principles of synaptic vesicle fusion is a long-sought goal. It requires the development of a synthetic system that allows manipulations and observations not possible in vivo. Here, we report an in vitro system with reconstituted synaptic proteins that meets the long-sought goal to produce fast content release in the millisecond time regime upon Ca(2+) triggering. Our system simultaneously monitors both content and lipid exchange, and it starts from stable interacting pairs of donor and acceptor vesicles, mimicking the readily releasable pool of synaptic vesicles prior to an action potential. It differentiates between single-vesicle interaction, hemifusion, and complete fusion, the latter mimicking quantized neurotransmitter release upon exocytosis of synaptic vesicles. Prior to Ca(2+) injection, the system is in a state in which spontaneous fusion events between donor and acceptor vesicles are rare. Upon Ca(2+) injection, a rapid burst of complete fusion events emerges, followed by a biphasic decay. The present study focuses on neuronal SNAREs, the Ca(2+) sensor synaptotagmin 1, and the modulator complexin. However, other synaptic proteins could be added and their function examined. Ca(2+) triggering is cooperative, requiring the presence of synaptotagmin, whereas SNAREs alone do not produce a fast fusion burst. Manipulations of the system mimic effects observed in vivo. These results also show that neuronal SNAREs alone do not efficiently produce complete fusion, that the combination of SNAREs with synaptotagmin lowers the activation barriers to full fusion, and that complexin enhances this kinetic control.
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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.