ArticleAmerican journal of physiology. Cell physiology2010
SV2 regulates neurotransmitter release via multiple mechanisms.
Article in American journal of physiology. Cell physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 138 citations in OpenAlex.
- Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials.Epilepsia · 2017Trial
- Structural Determinants of Synaptic Vesicle Protein 2C Ligand Selectivity and Their Impact on Dopamine Release.bioRxiv : the preprint server for biology · 2026Article
- Keratan Sulfate: An Electroconductive Glycosaminoglycan at the Interface of Sensory Perception and Neural Signaling.Journal of neuroscience research · 2026Review
- The Impact of Levetiracetam on Various Symptoms of Morphine Dependence in Mice.Life (Basel, Switzerland) · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Higher drinking frequency corresponds to lower synaptic density in people with alcohol use disorder.The Journal of clinical investigation · 2026Observational
- Mechanisms underlying allosteric modulation of antiseizure medication binding to synaptic vesicle protein 2A (SV2A).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Keratan Sulfate Is a Multifunctional Brain Glycosaminoglycan With Instructive Capabilities.Journal of neurochemistry · 2025Review
- New microRNA-based therapies reveal common targets in paediatric medulloblastoma and adult glioblastoma.Scientific reports · 2025Article
- Assessing non-invasive quantitative methods for [European journal of nuclear medicine and molecular imaging · 2025Article
- Structures of native SV2A reveal the binding mode for tetanus neurotoxin and anti-epileptic racetams.Nature communications · 2025Article
- Synaptophysin accelerates synaptic vesicle fusion by expanding the membrane upon neurotransmitter loading.Science advances · 2025Article
- Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties.International journal of molecular sciences · 2025Review
- Synaptic Vesicle Glycoprotein 2A Knockout in Parvalbumin and Somatostatin Interneurons Drives Seizures in the Postnatal Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Control of Synaptotagmin-1 Trafficking by SV2A-Mechanism and Consequences for Presynaptic Function and Dysfunction.Journal of neurochemistry · 2025Review
- Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.Nature structural & molecular biology · 2024Article
- Structural insights into SV2A and the mechanism of racetam anticonvulsants.Nature structural & molecular biology · 2024Article
- Functional genomics screens reveal a role for TBC1D24 and SV2B in antibody-dependent enhancement of dengue virus infection.Journal of virology · 2024Article
- Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Synaptic changes in psychiatric and neurological disorders: state-of-the art of in vivo imaging.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Among the proteins that mediate calcium-stimulated transmitter release, the synaptic vesicle protein 2 (SV2) stands out as a unique modulator specific to the neurons and endocrine cells of vertebrates. In synapses, SV2 regulates the expression and trafficking of the calcium sensor protein synaptotagmin, an action consistent with the reduced calcium-mediated exocytosis observed in neurons lacking SV2. Yet SV2 contains amino acid motifs consistent with it performing other actions that could regulate presynaptic functioning and that might underlie the mechanism of drug action. To test the role of these functional motifs, we performed a mutagenic analysis of SV2A and assessed the ability of mutant SV2A proteins to restore normal synaptic transmission in neurons from SV2A/B knockout mice. We report that SV2A-R231Q, harboring a mutation in a canonical transporter motif, restored normal synaptic depression (a measure of release probability and signature deficit of neurons lacking SV2). In contrast, normal synaptic depression was not restored by SV2A-W300A and SV2A-W666A, harboring mutations of conserved tryptophans in the 5th and 10th transmembrane domains. Although they did not rescue normal neurotransmission, SV2A-W300A and SV2A-W666A did restore normal levels of synaptotagmin expression and internalization. This indicates that tryptophans 300 and 666 support an essential action of SV2 that is unrelated to its role in synaptotagmin expression or trafficking. These results indicate that SV2 performs at least two actions at the synapse that contribute to neurotransmitter release.
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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.