Affinage

SV2A

Synaptic vesicle glycoprotein 2A · UniProt Q7L0J3

Audit flag: rerun needed
Length
742 aa
Mass
82.7 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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Mechanism profile

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Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 SV2A is a 12-transmembrane domain protein homologous to bacterial transporters, specifically to a family of proteins that transport sugars, citrate, and drugs; expression in COS cells yielded intracellular membrane localization consistent with a synaptic vesicle-specific transporter role. cDNA cloning, sequence analysis, heterologous expression in COS cells, immunolocalization Science High 1355409 1519064
1992 SV2A contains two sets of six predicted transmembrane domains: the N-terminal half homologous to glucose/sugar transporters and the C-terminal half homologous to plasma membrane neurotransmitter transporters, suggesting a role in neurotransmitter transport into synaptic vesicles. Sequence analysis of deduced amino acid sequence Cell High 1355409
1993 SV2A is a keratan sulfate proteoglycan; synaptic vesicles contain SV2 in two forms (H and L forms) distinguished by molecular mass, both carrying keratan sulfate glycosaminoglycan chains on the intravesicular side. Biochemical fractionation of electric organ synaptic vesicles, SDS-PAGE, immunoblotting, glycosaminoglycan characterization Journal of neurochemistry High 7685814
1994 SV2A is expressed ubiquitously throughout the brain in all synaptic vesicles; immunoprecipitation showed both SV2A and SV2B can coexist on the same synaptic vesicle. In situ hybridization, immunohistochemistry, isoform-specific immunoprecipitation followed by Western blot The Journal of Neuroscience High 8083732
1996 SV2A directly interacts with synaptotagmin in a calcium-regulated, isoform-specific manner: the interaction is specific to SV2A (not SV2B), is inhibited by calcium with an EC50 of ~10 µM, and is mediated by the cytoplasmic N-terminus of SV2A and the C2B domain of synaptotagmin. Cross-linking, co-immunoprecipitation, recombinant protein affinity chromatography The Journal of biological chemistry High 8910372
1996 SV2A is localized on the membranes of both synaptic vesicles and large dense-cored vesicles (LDCV) in PC12 cells, with a higher SV2:synaptophysin ratio on LDCVs than on synaptic vesicle clusters. Pre-embedding EM immunocytochemistry with silver-enhanced small gold probe The Journal of Histochemistry and Cytochemistry Medium 8985140
1999 SV2A knockout mice develop severe seizures and die within 3 weeks; loss of SV2A reduces action potential-dependent GABAergic neurotransmission in hippocampal CA3 without affecting action potential-independent (miniature) neurotransmission, establishing SV2A as essential for calcium-dependent exocytosis. Targeted gene disruption (knockout mice), electrophysiology of spontaneous IPSCs in hippocampal slices, synapse ultrastructure analysis PNAS High 10611374
2000 SV2A forms a complex with an alpha5-containing laminin (900-kDa laminin) on synaptosomes from electric organ, and purified SV2 binds with high affinity to laminin-1, suggesting SV2 acts as a laminin receptor on the presynaptic plasma membrane. Co-immunoprecipitation from synaptosomes, affinity chromatography with purified laminin-1, biochemical fractionation The Journal of biological chemistry Medium 10617638
2001 SV2A is required to maintain the readily releasable pool (RRP) of vesicles: adrenal chromaffin cells from SV2A knockout mice show a significantly reduced calcium-induced exocytotic burst (operationally defining the RRP), while burst kinetics are normal; loss of SV2A is also associated with fewer SDS-resistant SNARE complexes in brain. Direct capacitance measurements of exocytosis in chromaffin cells, SDS-PAGE analysis of SNARE complexes Nature Cell Biology High 11483953
2004 SV2A is the brain binding site for the antiepileptic drug levetiracetam: photoaffinity labeling of purified synaptic vesicles identifies the ~90 kDa LEV-binding protein as SV2A; brain membranes from SV2A knockout mice show no LEV binding; SV2A expressed in fibroblasts is sufficient for LEV binding; no binding occurs to SV2B or SV2C. Photoaffinity labeling, tritiated LEV derivative binding assays in SV2A knockout brain membranes, heterologous expression in fibroblasts, correlation between binding affinity and seizure protection PNAS High 15210974
2005 All three SV2 isoforms (SV2A, SV2B, SV2C) bind synaptotagmin at a common calcium-inhibited site; additionally, SV2A and SV2C (but not SV2B) possess a distinct N-terminal synaptotagmin-binding site that is stimulated by calcium, mapped to the first 57 amino acids; introduction of the SV2A/C N-terminus into cultured SCG neurons inhibited neurotransmission. Immunoprecipitation, recombinant protein binding assays, domain mapping, dominant-negative neuronal microinjection Molecular and Cellular Neurosciences High 15866046
2006 SV2 (isoforms A, B, and C) is the protein receptor for botulinum neurotoxin A (BoNT/A): BoNT/A binding to hippocampal neurons from SV2A/B knockout mice is abolished and restored by expressing any SV2 isoform; SV2 fragments containing the toxin interaction domain inhibit BoNT/A neuronal binding. BoNT/A binding assays in SV2 knockout neurons, rescue by viral expression of SV2 isoforms, competitive inhibition with SV2 fragments, reduced BoNT/A sensitivity in SV2B knockout mice Science High 16543415
2008 SV2A exists in two major structural conformations in situ: a compact funnel-structure with a pore-like opening toward the cytoplasm, and a more open V-shaped structure with a cleft toward the intravesicular space; levetiracetam binding does not lock SV2A into a specific conformational state. Protein Tomography of mouse brain tissue Biochemical and Biophysical Research Communications Low 18692481
2008 Glycosylated SV2A and SV2B act as protein receptors for BoNT/E: BoNT/E fails to enter SV2A/B knockout neurons; entry is restored by SV2A or SV2B but not SV2C; the fourth luminal domain (LD4) of SV2A/B is sufficient for BoNT/E binding and entry; disruption of an N-glycosylation site (N573Q) in SV2A abolishes BoNT/E entry and reduces BoNT/A entry; gangliosides are also required. BoNT entry assays in SV2A/B KO neurons, chimeric receptor rescue, site-directed mutagenesis of glycosylation sites, ganglioside depletion/rescue Molecular Biology of the Cell High 18815274
2009 SV2 renders primed synaptic vesicles competent for Ca2+-induced exocytosis: deletion of SV2 decreases evoked synaptic responses without changing mini frequency/amplitude, the RRP size, or apparent Ca2+ sensitivity of fusion, indicating SV2 acts at a post-priming step to make vesicles Ca2+/synaptotagmin-responsive; conserved charged residues in transmembrane regions and intravesicular glycosylation are required for normal SV2 folding/trafficking, while the putative synaptotagmin-binding sequence is dispensable. Electrophysiology in SV2 knockout neurons, rescue experiments with SV2 mutants, analysis of RRP and Ca2+ sensitivity The Journal of Neuroscience High 19176798
2009 BoNT/F uses all three isoforms of SV2 (SV2A, B, and C) as protein receptors, as demonstrated by co-precipitation of SV2A, B, and C from Triton-solubilized synaptic vesicles by BoNT/F, and by cross-competition assays and stimulation-dependent uptake in phrenic nerve preparations. Co-precipitation from synaptic vesicles, phrenic nerve hemidiaphragm assay, cross-competition with recombinant binding fragments, site-directed mutagenesis of ganglioside-binding site Journal of Neurochemistry High 19650874
2009 BoNT/F binds glycosylated SV2 through the keratan sulfate moiety; deglycosylation disrupts HCR/F interaction with synaptic vesicle glycoproteins; the HCR/F binding site on SV2 is distinct from that of BoNT/B on synaptotagmin. Crystal structure of HCR/F and HCR/A, solid-phase array glycan binding, affinity chromatography, deglycosylation enzymes, site-directed mutagenesis Biochemistry High 19476346
2010 SV2A regulates synaptotagmin expression and trafficking via a tyrosine-based endocytosis motif (Y46) in its cytoplasmic N-terminus: disruption of this motif (Y46A mutant) prevents SV2A internalization, fails to restore normal synaptotagmin plasma membrane distribution, and reduces binding to clathrin adaptors AP2, EPS15, and amphiphysin 2/Bin1; neurons lacking SV2 have less synaptotagmin in synaptic vesicles. Mutagenesis, live imaging, in vitro binding assays, immunoisolation of synaptic vesicles from SV2A/B double KO mice, electrophysiology rescue experiments The Journal of Neuroscience High 20410110
2010 SV2 regulates neurotransmitter release through at least two independent mechanisms: (1) regulating synaptotagmin expression/trafficking (disrupted by loss of conserved tryptophans W300 and W666 in transmembrane domains 5 and 10), and (2) a separate action unrelated to synaptotagmin (the canonical transporter motif R231Q restores normal synaptic depression without affecting synaptotagmin). Site-directed mutagenesis of SV2A, electrophysiological rescue in SV2A/B knockout neurons, synaptotagmin expression and internalization assays American Journal of Physiology – Cell Physiology High 20702688
2010 SV2 (specifically SV2B) controls key aspects of synaptic function via regulation of presynaptic Ca2+: loss of SV2B elevates both resting and evoked presynaptic Ca2+ signals; short-term reproduction of the Ca2+ phenotype in wild-type terminals reproduces the SV2B-/- secretory phenotype; rescue of Ca2+ phenotype in SV2B-/- neurons relieves all aspects of the secretory phenotype. Direct presynaptic Ca2+ measurements (fluorescent indicators), capacitance measurements, pharmacological Ca2+ manipulation in the goldfish Mb1 bipolar cell terminal, SV2B knockout mice Neuron High 20620874
2010 SV2A and SV2B mediate binding and entry of tetanus neurotoxin into central neurons: tetanus toxin cannot cleave synaptobrevin II in SV2 knockout neurons; entry is rescued by viral expression of SV2A or SV2B; SV2B is preferentially localized to excitatory terminals while SV2A is preferentially at inhibitory terminals in cortical neurons. Tetanus toxin intoxication assays in SV2 KO neurons, viral rescue, immunolocalization of SV2 isoforms in excitatory vs inhibitory terminals PLoS Pathogens High 21124874
2011 SV2 (all three isoforms) serves as the protein receptor for BoNT/D: BoNT/D enters neurons via synaptic vesicle recycling, can bind SV2 in brain detergent extracts, and fails to bind/enter SV2-null neurons; rescue is achieved by any of SV2A, B, or C; BoNT/D uses a mechanism distinct from BoNT/A and BoNT/E since chimeric receptors with BoNT/A/E binding sites cannot mediate BoNT/D entry; gangliosides are also essential. Toxin binding and intoxication assays in SV2 KO neurons, viral rescue with individual isoforms, co-precipitation from brain extracts, ganglioside depletion PLoS Pathogens High 21483489
2011 Levetiracetam reverses the synaptic deficit caused by SV2A overexpression: excess SV2A (~1.5-fold) in autaptic hippocampal neurons reduces release probability and increases synaptotagmin levels; LEV treatment restores normal neurotransmission and normalizes SV2 and synaptotagmin levels at the synapse. Autaptic hippocampal neuron culture, SV2A-EGFP overexpression, electrophysiology, LEV pharmacology, immunocytochemistry PLoS One Medium 22220214
2012 SV2A-deficient (but not SV2B-deficient) mice show increased frequency of spontaneous excitatory postsynaptic currents and decreased frequency/amplitude of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons; miniature (action potential-independent) EPSCs and IPSCs are unaffected, indicating SV2A specifically regulates action potential- and Ca2+-dependent transmission. Whole-cell patch-clamp electrophysiology in hippocampal slices from SV2A KO, SV2B KO, and SV2A/B double KO mice Journal of Neuroscience Research High 22847229
2012 N-glycosylation is required for synaptic targeting and function of SV2A: mutation of N-glycosylation sites on SV2A causes only partial mistargeting (N-glycans on SV2A are only partially dispensable), in contrast to synaptophysin where N-glycosylation is essential; glycosylation of synaptotagmin 1 is completely dispensable for SV2 sorting. Site-directed mutagenesis of all glycosylation sites, pHluorin-tagged protein imaging in cultured neurons from KO mice The Journal of biological chemistry High 22908222
2013 UCB1244283 acts as a positive allosteric modulator of SV2A: it increases the affinity of UCB30889 for SV2A fivefold and doubles the total number of binding sites, slows association and dissociation kinetics, and exerts anticonvulsant effects in vivo, indicating that SV2A conformation can be modulated allosterically. Radioligand binding assays (saturation and competition) on recombinant human SV2A in HEK cells and rat cortex, kinetic binding assays, in vivo audiogenic seizure model British Journal of Pharmacology Medium 23530581
2013 The SV2A-binding interface for BoNT/E maps to a site corresponding to the synaptotagmin-binding region of BoNT/B plus an extended surface comprising N- and C-terminal halves of the BoNT/E binding domain; mutations at this interface reduce both SV2 binding and neurotoxicity; a neutralizing antibody inhibits BoNT/E by directly blocking the BoNT/E-SV2 interaction. Site-directed mutagenesis, pull-down binding assays, phrenic nerve hemidiaphragm neurotoxicity assay, antibody neutralization The Biochemical Journal High 23621114
2014 Human SV2A functions as a galactose transporter when expressed in hexose transport-deficient yeast (EBY.VW4000): cells expressing SV2A grow on galactose medium but not other carbon sources; direct measurement confirms galactose uptake; levetiracetam inhibits this galactose-dependent growth, linking drug binding to transporter function. Heterologous expression in hexose transport-deficient yeast, growth assay on galactose medium, direct radiolabeled galactose uptake measurement, pharmacological inhibition by LEV The Journal of biological chemistry High 25326386
2015 SV2A and stonin 2 (Stn2) have overlapping activities in endocytic sorting of synaptotagmin 1 (Syt1) to synaptic vesicles: deletion of either alone causes partial Syt1 missorting, while deletion of both dramatically exacerbates Syt1 loss and missorting, impairing neurotransmission efficacy. Genetic deletion (SV2A/B KO and Stn2 KO/knockdown), live fluorescence microscopy, electrophysiology in hippocampal synapses PNAS High 26015569
2015 Homology modeling and site-directed mutagenesis identified residues lining the levetiracetam binding pocket in SV2A; mutation of D670 leads to complete loss of LEV analog binding, confirming its role in the binding site. Homology modeling, molecular dynamics simulation, site-directed mutagenesis, radioligand binding assay PLoS One Medium 25692762
2016 N-linked glycosylation of SV2C is essential for BoNT/A1 binding and neuronal uptake: the crystal structure (2.0 Å) of the BoNT/A1 receptor-binding domain complexed with glycosylated human SV2C reveals that BoNT/A1 recognizes both the protein moiety and a conserved N-linked glycan on SV2; this glycan is required for potent neurotoxicity. X-ray crystallography (2.0-Å resolution structure), mutagenesis of glycosylation sites, neuronal binding and toxicity assays Nature Structural & Molecular Biology High 27294781
2016 SV2A luminal domain 4 (LD4) binds BoNT/A with isoform-dependent affinity (SV2C >> SV2A > SV2B); binding constant of ~200 nM for BoNT/A to rat SV2C-LD4; binding affinity increases >10-fold at pH 5 (acidic vesicle conditions); the quadrilateral β-helix of SV2C-LD4 pre-exists in solution before toxin binding, unlike the conformational change seen in the BoNT/B-synaptotagmin interaction. GST pull-down assay, surface plasmon resonance, circular dichroism spectroscopy, pH-dependent binding assays Toxins High 27196927
2016 A missense mutation in SV2A (L174Q) specifically reduces depolarization-induced GABA (but not glutamate) release in the hippocampus, reduces synaptotagmin 1 levels, and facilitates kindling epileptogenesis; SV2A is predominantly expressed in GABAergic neurons. Rat knockin model (Sv2aL174Q), neurochemical measurement of GABA/glutamate release, Western blot for synaptic proteins, kindling model, immunohistochemistry Scientific Reports High 27265781
2016 SV2A dysfunction (Sv2aL174Q mutation) elevates seizure susceptibility by preferentially disrupting synaptic GABA release in the amygdala, with SV2A predominantly expressed in GABAergic neurons co-stained for glutamate decarboxylase 1; in vivo microdialysis confirms specific reduction of evoked GABA but not glutamate release. Rat knockin model, in vivo microdialysis, Fos mapping, immunofluorescence double-labeling Frontiers in Pharmacology High 27471467
2020 The epilepsy-linked human SV2A mutation R383Q causes mislocalization of SV2A from synaptic vesicles to the plasma membrane, reduces binding to synaptotagmin-1 (Syt1), and fails to rescue reduced Syt1 expression and dysfunctional activity-dependent Syt1 trafficking in SV2A-depleted neurons. Molecular replacement strategy in mouse neuronal cultures depleted of endogenous SV2A, live fluorescence imaging of SV2A localization and activity-dependent trafficking, co-immunoprecipitation for Syt1 binding The Journal of Neuroscience High 32341095
2020 SV2A coordinates distinct synaptic vesicle recycling rates between excitatory and inhibitory synapses: SV2A is more highly expressed in inhibitory synapses and mediates slower SV recycling (~1.8-fold) in inhibitory vs excitatory terminals, with differential control of synaptotagmin I sorting. pHluorin-conjugated SV-specific tracers preferentially expressed in excitatory or inhibitory terminals, live imaging of SV recycling kinetics, SV2A knockdown Progress in Neurobiology Medium 32615146
2020 Poly-glycine-alanine (GA) dipeptide repeat proteins from C9orf72-ALS/FTD cause reduction in SV2 protein levels and alter Ca2+ influx and synaptic vesicle release; restoring SV2 levels corrects these synaptic phenotypes. GA mouse model, iPSC-derived neurons from patients, SV2 overexpression rescue, Ca2+ imaging, synaptic vesicle release assays EMBO Molecular Medicine Medium 32347002
2020 SV2A expression is regulated post-transcriptionally by miR-133a and miR-218: luciferase reporter assays demonstrate that both miRNAs significantly decrease SV2A 3'UTR-driven expression; transfection of miR-133a and miR-218 reduces endogenous SV2A mRNA and protein in human neuroblastoma cells. Dual-luciferase reporter assay with SV2A 3'UTR construct, miRNA transfection, RT-qPCR and Western blot of endogenous SV2A Translational Psychiatry Medium 32839459
2023 BoNT/A targeted endocytosis into synaptic vesicles requires simultaneous binding to a tripartite plasma membrane nanocluster of polysialoganglioside (PSG), synaptotagmin-1 (Syt1), and SV2; BoNT/A interacts with the preassembled PSG-Syt1 complex and SV2 concurrently, facilitating Syt1-SV2 nanoclustering that controls endocytic sorting into synaptic vesicles. Live-cell super-resolution imaging, electron microscopy, catalytically inactivated BoNT/A wildtype and receptor-binding-deficient mutants in hippocampal neurons, Syt1 CRISPRi knockdown with SNAP-25 cleavage readout The EMBO Journal High 37226896
2024 Cryo-EM structures of full-length SV2A in complex with BoNT/A2 HC and either levetiracetam or brivaracetam reveal: (1) the large fourth luminal domain of SV2A binds BoNT/A2 HC through protein-protein and protein-glycan interactions; (2) LEV and BRV occupy the putative substrate-binding site in an outward-open conformation; (3) a propyl group in BRV creates additional contacts with SV2A explaining its higher affinity than LEV. Cryo-electron microscopy structure determination of full-length SV2A complexes, label-free spectral shift assay for binding affinity Nature Communications High 38637505

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proceedings of the National Academy of Sciences of the United States of America 1085 15210974
2006 SV2 is the protein receptor for botulinum neurotoxin A. Science (New York, N.Y.) 579 16543415
1999 Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A). Proceedings of the National Academy of Sciences of the United States of America 340 10611374
1994 Differential expression of synaptic vesicle protein 2 (SV2) isoforms. The Journal of neuroscience : the official journal of the Society for Neuroscience 324 8083732
1992 The synaptic vesicle protein SV2 is a novel type of transmembrane transporter. Cell 246 1355409
1992 SV2, a brain synaptic vesicle protein homologous to bacterial transporters. Science (New York, N.Y.) 224 1519064
2008 Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons. Molecular biology of the cell 194 18815274
2011 Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. European journal of pharmacology 185 21575627
2008 Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A. British journal of pharmacology 184 18500360
2020 Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats. Nature communications 179 31937764
2001 SV2 modulates the size of the readily releasable pool of secretory vesicles. Nature cell biology 173 11483953
2009 SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 141 19176798
2010 Cotrafficking of SV2 and synaptotagmin at the synapse. The Journal of neuroscience : the official journal of the Society for Neuroscience 133 20410110
2007 SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy. Neuropharmacology 132 18207204
1996 Isoform-specific, calcium-regulated interaction of the synaptic vesicle proteins SV2 and synaptotagmin. The Journal of biological chemistry 131 8910372
2009 Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding site prior to stimulation-dependent uptake with botulinum neurotoxin F utilising the three isoforms of SV2 as second receptor. Journal of neurochemistry 127 19650874
2015 Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 125 26663401
2006 Binding characteristics of levetiracetam to synaptic vesicle protein 2A (SV2A) in human brain and in CHO cells expressing the human recombinant protein. European journal of pharmacology 122 16556440
2009 Glycosylated SV2 and gangliosides as dual receptors for botulinum neurotoxin serotype F. Biochemistry 121 19476346
2016 Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia 119 26920914
2010 SV2 regulates neurotransmitter release via multiple mechanisms. American journal of physiology. Cell physiology 117 20702688
2011 Botulinum neurotoxin D uses synaptic vesicle protein SV2 and gangliosides as receptors. PLoS pathogens 112 21483489
2010 SV2 mediates entry of tetanus neurotoxin into central neurons. PLoS pathogens 99 21124874
2010 SV2 acts via presynaptic calcium to regulate neurotransmitter release. Neuron 96 20620874
2007 Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug metabolism and disposition: the biological fate of chemicals 95 17908923
2016 N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A. Nature structural & molecular biology 92 27294781
2009 Proepileptic phenotype of SV2A-deficient mice is associated with reduced anticonvulsant efficacy of levetiracetam. Epilepsia 92 19486357
1993 The SV2 protein of synaptic vesicles is a keratan sulfate proteoglycan. Journal of neurochemistry 92 7685814
2018 Quantifying SV2A density and drug occupancy in the human brain using [11C]UCB-J PET imaging and subcortical white matter as reference tissue. European journal of nuclear medicine and molecular imaging 81 30121895
2005 SV2A and SV2C contain a unique synaptotagmin-binding site. Molecular and cellular neurosciences 73 15866046
1993 The synaptic vesicle proteins SV2, synaptotagmin and synaptophysin are sorted to separate cellular compartments in CHO fibroblasts. The Journal of cell biology 71 7901222
1996 Subcellular localization of SV2 and other secretory vesicle components in PC12 cells by an efficient method of preembedding EM immunocytochemistry for cell cultures. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 62 8985140
1994 Light and electron microscopic analysis of synaptic development in Macaca monkey retina as detected by immunocytochemical labeling for the synaptic vesicle protein, SV2. The Journal of comparative neurology 60 8144745
2014 Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis. Neuropathology and applied neurobiology 59 23617838
1989 Most synaptic vesicles isolated from rat brain carry three membrane proteins, SV2, synaptophysin, and p65. Journal of neurochemistry 59 2496198
2015 Overlapping functions of stonin 2 and SV2 in sorting of the calcium sensor synaptotagmin 1 to synaptic vesicles. Proceedings of the National Academy of Sciences of the United States of America 57 26015569
2022 Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular psychiatry 56 35165397
2016 Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission. Scientific reports 55 27265781
2014 Discovery of heterocyclic nonacetamide synaptic vesicle protein 2A (SV2A) ligands with single-digit nanomolar potency: opening avenues towards the first SV2A positron emission tomography (PET) ligands. ChemMedChem 55 24446373
2019 Development and In Vivo Preclinical Imaging of Fluorine-18-Labeled Synaptic Vesicle Protein 2A (SV2A) PET Tracers. Molecular imaging and biology 54 30084043
2011 Levetiracetam reverses synaptic deficits produced by overexpression of SV2A. PloS one 52 22220214
2016 A Mitochondrial Role of SV2a Protein in Aging and Alzheimer's Disease: Studies with Levetiracetam. Journal of Alzheimer's disease : JAD 50 26639968
2013 Expression of SV2 isoforms during rodent brain development. BMC neuroscience 49 23937191
2005 SV2A and SV2C are not vesicular Ca2+ transporters but control glucose-evoked granule recruitment. Journal of cell science 49 16306227
2007 Levetiracetam: the first SV2A ligand for the treatment of epilepsy. Expert opinion on drug discovery 45 23484603
2000 The synaptic vesicle protein SV2 is complexed with an alpha5-containing laminin on the nerve terminal surface. The Journal of biological chemistry 45 10617638
2014 The human synaptic vesicle protein, SV2A, functions as a galactose transporter in Saccharomyces cerevisiae. The Journal of biological chemistry 44 25326386
2020 Synaptic dysfunction induced by glycine-alanine dipeptides in C9orf72-ALS/FTD is rescued by SV2 replenishment. EMBO molecular medicine 43 32347002
2012 Glycosylation is dispensable for sorting of synaptotagmin 1 but is critical for targeting of SV2 and synaptophysin to recycling synaptic vesicles. The Journal of biological chemistry 43 22908222
2019 Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A). European journal of nuclear medicine and molecular imaging 42 31175396
2015 Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [(18)F]UCB-H: First-in-Human Study. Molecular imaging and biology 40 25595813
2014 Radiosynthesis of (11)C-Levetiracetam: A Potential Marker for PET Imaging of SV2A Expression. ACS medicinal chemistry letters 39 25313330
2013 Identification of the SV2 protein receptor-binding site of botulinum neurotoxin type E. The Biochemical journal 39 23621114
2009 Preferential increase in the hippocampal synaptic vesicle protein 2A (SV2A) by pentylenetetrazole kindling. Biochemical and biophysical research communications 36 19751703
2020 Distinct synaptic vesicle recycling in inhibitory nerve terminals is coordinated by SV2A. Progress in neurobiology 35 32615146
2012 Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A-deficient but not SV2B-deficient mice. Journal of neuroscience research 34 22847229
2010 The SV2 variant of KLF6 is down-regulated in hepatocellular carcinoma and displays anti-proliferative and pro-apoptotic functions. Journal of hepatology 34 20801538
2013 Preclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H. EJNMMI research 33 23647774
1993 Conservation of the amino acid sequence of SV2, a transmembrane transporter in synaptic vesicles and endocrine cells. Gene 33 8299963
2012 Analysis of Synaptotagmin, SV2, and Rab3 Expression in Cortical Glutamatergic and GABAergic Axon Terminals. Frontiers in cellular neuroscience 32 22275882
2019 Increased Inflammation and Unchanged Density of Synaptic Vesicle Glycoprotein 2A (SV2A) in the Postmortem Frontal Cortex of Alzheimer's Disease Patients. Frontiers in cellular neuroscience 31 31866830
2013 Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain. Molecular & cellular proteomics : MCP 31 24284412
2011 Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model. PloS one 31 22046416
2011 Increased levels of SV2A botulinum neurotoxin receptor in clinical sensory disorders and functional effects of botulinum toxins A and E in cultured human sensory neurons. Journal of pain research 31 22090803
2018 SV2: accurate structural variation genotyping and de novo mutation detection from whole genomes. Bioinformatics (Oxford, England) 30 29300834
2020 In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PET. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 29 32538280
2016 Botulinum Neurotoxin Serotype A Recognizes Its Protein Receptor SV2 by a Different Mechanism than Botulinum Neurotoxin B Synaptotagmin. Toxins 29 27196927
1998 Synaptic vesicle protein SV2B, but not SV2A, is predominantly expressed and associated with microvesicles in rat pinealocytes. Journal of neurochemistry 28 9648885
2020 An Epilepsy-Associated SV2A Mutation Disrupts Synaptotagmin-1 Expression and Activity-Dependent Trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 32341095
2016 A Missense Mutation of the Gene Encoding Synaptic Vesicle Glycoprotein 2A (SV2A) Confers Seizure Susceptibility by Disrupting Amygdalar Synaptic GABA Release. Frontiers in pharmacology 26 27471467
2008 No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy. Epilepsy research 26 18977120
2024 Tracing synaptic loss in Alzheimer's brain with SV2A PET-tracer UCB-J. Alzheimer's & dementia : the journal of the Alzheimer's Association 25 38363009
2011 Insecticidal potency of bacterial species Bacillus thuringiensis SV2 and Serratia nematodiphila SV6 against larvae of mosquito species Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. Parasitology research 25 22065062
2008 Visualization of SV2A conformations in situ by the use of Protein Tomography. Biochemical and biophysical research communications 25 18692481
2023 Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG-Syt1-SV2 plasma membrane nanocluster for synaptic vesicle entry. The EMBO journal 24 37226896
2020 Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular imaging and biology 24 33258040
2017 Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis. CNS & neurological disorders drug targets 24 28393712
2015 Exploring the interaction of SV2A with racetams using homology modelling, molecular dynamics and site-directed mutagenesis. PloS one 23 25692762
2013 Modulation of the conformational state of the SV2A protein by an allosteric mechanism as evidenced by ligand binding assays. British journal of pharmacology 23 23530581
2012 Kindling-associated SV2A expression in hilar GABAergic interneurons of the mouse dentate gyrus. Neuroscience letters 23 22266237
2002 Expression of synaptic vesicle protein 2 (SV2) in neuroendocrine tumours of the gastrointestinal tract and pancreas. The Journal of pathology 23 11748641
1996 Mapping the innervation of the bronchial tree in fetal and postnatal pig lung using antibodies to PGP 9.5 and SV2. American journal of respiratory cell and molecular biology 23 8969263
2019 Differential expression of SV2A in hippocampal glutamatergic and GABAergic terminals during postnatal development. Brain research 22 30905653
2018 Expression of KLF6-SV2 in colorectal cancer and its impact on proliferation and apoptosis. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 22 29084019
2002 Neoplastic transformation of human lung fibroblast MRC-5 SV2 cells induced by benzo[a]pyrene and confluence culture. Cancer research 22 12183415
2020 Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy. Molecular imaging and biology 21 32206990
2023 Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil. Neuroscience bulletin 20 37897555
2024 SV2A PET imaging in human neurodegenerative diseases. Frontiers in aging neuroscience 18 38699560
2014 Hippocampal low-frequency stimulation increased SV2A expression and inhibited the seizure degree in pharmacoresistant amygdala-kindling epileptic rats. Epilepsy research 18 25205164
2024 Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment. Alzheimer's & dementia : the journal of the Alzheimer's Association 17 38634334
2019 Mode of seizure inhibition by sodium channel blockers, an SV2A ligand, and an AMPA receptor antagonist in a rat amygdala kindling model. Epilepsy research 16 31035244
2023 Longitudinal Imaging of Regional Brain Volumes, SV2A, and Glucose Metabolism In Huntington's Disease. Movement disorders : official journal of the Movement Disorder Society 15 37382295
2024 Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A. Nature communications 14 38637505
2021 Validation of SV2A-Targeted PET Imaging for Noninvasive Assessment of Neuroendocrine Differentiation in Prostate Cancer. International journal of molecular sciences 14 34884893
2020 Integration of postmortem amygdala expression profiling, GWAS, and functional cell culture assays: neuroticism-associated synaptic vesicle glycoprotein 2A (SV2A) gene is regulated by miR-133a and miR-218. Translational psychiatry 14 32839459
2019 Levetiracetam-induced a new seizure type in a girl with a novel SV2A gene mutation. Clinical neurology and neurosurgery 14 31005049
2016 Development and Validation of a New Mouse Model to Investigate the Role of SV2A in Epilepsy. PloS one 14 27861538
2018 Preparation of 99mTc-levetiracetam intranasal microemulsion as the first radiotracer for SPECT imaging of the Synaptic Vesicle Protein SV2A. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 13 29787786
2012 Genetic variation at the synaptic vesicle gene SV2A is associated with schizophrenia. Schizophrenia research 13 23017826
2009 SV2 frustrating exocytosis at the semi-diffusor synapse. Synapse (New York, N.Y.) 13 19140166