High-resolution electron cryomicroscopy of V-ATPase in native synaptic vesicles
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Abstract
Intercellular communication in the nervous system occurs through the release of neurotransmitters into the synaptic cleft between neurons. In the presynaptic neuron, the proton pumping vesicular- or vacuolar-type ATPase (V-ATPase) powers neurotransmitter loading into synaptic vesicles (SVs), with the V 1 complex dissociating from the membrane region of the enzyme before exocytosis. We isolated SVs from rat brain using SidK, a V-ATPase–binding bacterial effector protein. Single-particle electron cryomicroscopy allowed high-resolution structure determination of V-ATPase within the native SV membrane. In the structure, regularly spaced cholesterol molecules decorate the enzyme’s rotor and the abundant SV protein synaptophysin binds the complex stoichiometrically. ATP hydrolysis during vesicle loading results in a loss of the V 1 region of V-ATPase from the SV membrane, suggesting that loading is sufficient to induce dissociation of the enzyme.
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- Authors
- Coupland, C. E., Karimi, R., Bueler, S. A., Liang, Y., Courbon, G. M., Di Trani, J. M., Wong, C. J., Saghian, R., Youn, J.-Y., Wang, L.-Y., & Rubinstein, J. L.
- Affiliations
- Great Ormond Street Hospital (GB)
- University of Toronto (CA)
- Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 1X1, Canada.
- Lunenfeld-Tanenbaum Research Institute (CA)
- Corresponding author
- Rubinstein, John L.
- ORCID
- Venue
- Science
- Published
- 2024-07-12
- Volume
- 385
- Issue
- 6705
- Pages
- 168-174
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4399848824
- Cited by
- 58
- References
- 5
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 9 · 2023: 1
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Canada Research Chairs
- University of Toronto
- Hospital for Sick Children
- Canadian Institutes of Health Research (66152_1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- V-ATPase, synaptic vesicles, proton pump, neurotransmitter release, synaptophysin, cholesterol, ATP hydrolysis, vesicle loading, presynaptic neurons, vesicle membrane
- MeSH terms
- Adenosine Triphosphate, Animals, Bacterial Proteins, Brain, Cholesterol, Hydrolysis, Protein Conformation, Synaptic Vesicles, Synaptophysin, Cryoelectron Microscopy, Vacuolar Proton-Translocating ATPases, Rats
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