Gene Symbol: Sv2a
Description: synaptic vesicle glycoprotein 2 a
Alias: AI746429, mKIAA0736, synaptic vesicle glycoprotein 2A, calcium regulator SV2A, synaptic vesicle protein 2, synaptic vesicle protein 2A
Species: mouse
Products:     Sv2a

Top Publications

  1. Xu T, Bajjalieh S. SV2 modulates the size of the readily releasable pool of secretory vesicles. Nat Cell Biol. 2001;3:691-8 pubmed
    ..Here we show that Synaptic Vesicle Protein 2 (SV2), a protein specific to neurons and endocrine cells, is required to maintain a pool of vesicles ..
  2. Gautam M, Noakes P, Moscoso L, Rupp F, Scheller R, Merlie J, et al. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell. 1996;85:525-35 pubmed
  3. Custer K, Austin N, Sullivan J, Bajjalieh S. Synaptic vesicle protein 2 enhances release probability at quiescent synapses. J Neurosci. 2006;26:1303-13 pubmed
    We report a thorough analysis of neurotransmission in cultured hippocampal neurons lacking synaptic vesicle protein 2 (SV2), a membrane glycoprotein present in all vesicles that undergo regulated secretion...
  4. Dong M, Liu H, Tepp W, Johnson E, Janz R, Chapman E. Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons. Mol Biol Cell. 2008;19:5226-37 pubmed publisher
    ..Here we identified two isoforms of the synaptic vesicle protein SV2, SV2A and SV2B, as the protein receptors for BoNT/E...
  5. Newell Litwa K, Salazar G, Smith Y, Faundez V. Roles of BLOC-1 and adaptor protein-3 complexes in cargo sorting to synaptic vesicles. Mol Biol Cell. 2009;20:1441-53 pubmed publisher
    ..Our results demonstrate that lysosomal and lysosome-related organelle biogenesis mechanisms regulate steady-state synaptic vesicle protein composition from shared early endosomes. ..
  6. Janz R, Goda Y, Geppert M, Missler M, Sudhof T. SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release. Neuron. 1999;24:1003-16 pubmed
    SV2 proteins are abundant synaptic vesicle proteins expressed in two major (SV2A and SV2B) and one minor isoform (SV2C) that resemble transporter proteins...
  7. Crowder K, Gunther J, Jones T, Hale B, Zhang H, Peterson M, et al. Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A). Proc Natl Acad Sci U S A. 1999;96:15268-73 pubmed
    b>Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles...
  8. Chang W, Sudhof T. SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis. J Neurosci. 2009;29:883-97 pubmed publisher
    b>Synaptic vesicle protein 2 (SV2), one of the first synaptic vesicle proteins identified, is characterized by multiple transmembrane regions that exhibit homology to sugar transporters, and by a highly glycosylated intravesicular sequence...
  9. Nowack A, Yao J, Custer K, Bajjalieh S. SV2 regulates neurotransmitter release via multiple mechanisms. Am J Physiol Cell Physiol. 2010;299:C960-7 pubmed publisher
    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...

More Information


  1. Wang M, Janz R, Belizaire R, Frishman L, Sherry D. Differential distribution and developmental expression of synaptic vesicle protein 2 isoforms in the mouse retina. J Comp Neurol. 2003;460:106-22 pubmed
    b>Synaptic vesicle protein 2 (SV2), a ubiquitous synaptic vesicle protein, is known to participate in the regulation of Ca(2+)-mediated synaptic transmission, although its precise function has not been established...
  2. Yao J, Nowack A, Kensel Hammes P, Gardner R, Bajjalieh S. Cotrafficking of SV2 and synaptotagmin at the synapse. J Neurosci. 2010;30:5569-78 pubmed publisher
    ..Aberrant neurotransmission in cultured hippocampal neurons lacking SV2 was rescued by expression of wild-type SV2A, but not by SV2A-Y46A, a mutant containing a disrupted endocytosis motif in SV2A's cytoplasmic N terminus...
  3. Serpinskaya A, Feng G, Sanes J, Craig A. Synapse formation by hippocampal neurons from agrin-deficient mice. Dev Biol. 1999;205:65-78 pubmed
    ..These results indicate that the z+ forms of agrin are dispensable for glutamatergic and GABAergic synaptic differentiation in the central nervous system. ..
  4. Venkatesan K, Alix P, Marquet A, Doupagne M, Niespodziany I, Rogister B, et al. Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A-deficient but not SV2B-deficient mice. J Neurosci Res. 2012;90:2317-27 pubmed publisher
    b>Synaptic vesicle protein 2 (SV2) is a glycoprotein that exists in three isoforms, SV2A, SV2B, and SV2C...
  5. Dong M, Yeh F, Tepp W, Dean C, Johnson E, Janz R, et al. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006;312:592-6 pubmed
    ..BoNT/A binding to SV2A and SV2B knockout hippocampal neurons was abolished and was restored by expressing SV2A, SV2B, or SV2C...
  6. Ohno Y, Okumura T, Terada R, Ishihara S, Serikawa T, Sasa M. Kindling-associated SV2A expression in hilar GABAergic interneurons of the mouse dentate gyrus. Neurosci Lett. 2012;510:93-8 pubmed publisher
    Immunohistochemical studies were performed to analyze the expressional changes in hippocampal synaptic vesicle protein 2A (SV2A) following pentylenetetrazole (PTZ) kindling...
  7. Crèvecœur J, Foerch P, Doupagne M, Thielen C, Vandenplas C, Moonen G, et al. Expression of SV2 isoforms during rodent brain development. BMC Neurosci. 2013;14:87 pubmed publisher
    b>SV2A, SV2B and SV2C are synaptic vesicle proteins that are structurally related to members of the major facilitator superfamily (MFS)...
  8. Chen J, Billings S, Nishimune H. Calcium channels link the muscle-derived synapse organizer laminin ?2 to Bassoon and CAST/Erc2 to organize presynaptic active zones. J Neurosci. 2011;31:512-25 pubmed publisher
    ..These results suggest that presynaptic VDCCs link the target-derived synapse organizer laminin ?2 to active-zone proteins and function as scaffolding proteins to anchor active-zone proteins to the presynaptic membrane. ..
  9. Weiner J, Koo S, Nicolas S, Fraboulet S, Pfaff S, Pourquie O, et al. Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1. Mol Cell Neurosci. 2004;27:59-69 pubmed
    ..Together, these results demonstrate that BEN promotes fasciculation of multiple axonal populations and uncover an unexpected function for BEN in retinal histogenesis...
  10. Ross J, Webster R, Lechertier T, Reynolds L, Turmaine M, Bencze M, et al. Multiple roles of integrin-α3 at the neuromuscular junction. J Cell Sci. 2017;130:1772-1784 pubmed publisher
    ..These results demonstrate multiple roles of integrin-α3 at the NMJ, and suggest that alterations in its function could underlie defects that occur in neurodegeneration or ageing. ..
  11. Noakes P, Chin D, Kim S, Liang S, Phillips W. Expression and localisation of dynamin and syntaxin during neural development and neuromuscular synapse formation. J Comp Neurol. 1999;410:531-40 pubmed
    ..The delayed appearance of dynamin at the synapse, thus, heralds the neonatal development of robust synaptic transmission at the neuromuscular junction. ..
  12. Chaverra M, George L, Mergy M, Waller H, Kujawa K, Murnion C, et al. The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system. Dis Model Mech. 2017;10:605-618 pubmed publisher
    ..With the identification of discrete CNS cell types and structures that depend on Ikbkap, novel strategies to thwart the progressive demise of CNS neurons in FD can be developed. ..
  13. Krishnaswamy A, Yamagata M, Duan X, Hong Y, Sanes J. Sidekick 2 directs formation of a retinal circuit that detects differential motion. Nature. 2015;524:466-470 pubmed publisher
    ..This non-canonical circuit introduces a delay into the pathway from photoreceptors in the centre of the receptive field to W3B-RGCs, which could improve their ability to judge the synchrony of local and global motion. ..
  14. Misgeld T, Burgess R, Lewis R, Cunningham J, Lichtman J, Sanes J. Roles of neurotransmitter in synapse formation: development of neuromuscular junctions lacking choline acetyltransferase. Neuron. 2002;36:635-48 pubmed
    ..At subsequent stages, neurotransmission delays some steps in synaptic maturation but accelerates others. Thus, neurotransmission affects synaptogenesis from early stages and coordinates rather than drives synaptic maturation. ..
  15. Kaempf N, Kochlamazashvili G, Puchkov D, Maritzen T, Bajjalieh S, Kononenko N, et al. Overlapping functions of stonin 2 and SV2 in sorting of the calcium sensor synaptotagmin 1 to synaptic vesicles. Proc Natl Acad Sci U S A. 2015;112:7297-302 pubmed publisher
    ..sensor synaptotagmin 1 (Syt1) is mediated by the overlapping activities of the Syt1-associated SV glycoprotein SV2A/B and the endocytic Syt1-adaptor stonin 2 (Stn2)...
  16. Yap K, Lim Z, Khandelia P, Friedman B, Makeyev E. Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention. Genes Dev. 2012;26:1209-23 pubmed publisher
    ..We propose that this mechanism counters ectopic and precocious expression of functionally linked neuron-specific genes and ensures their coherent activation in the appropriate developmental context. ..
  17. Liang S, Motin L, Moussa C, Lavidis N, Phillips W. Spatial distribution and developmental appearance of postjunctional P2X1 receptors on smooth muscle cells of the mouse vas deferens. Synapse. 2001;42:1-11 pubmed
  18. Weatherbee S, Anderson K, Niswander L. LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction. Development. 2006;133:4993-5000 pubmed
    ..The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes. ..
  19. Carpanini S, McKie L, Thomson D, Wright A, Gordon S, Roche S, et al. A novel mouse model of Warburg Micro syndrome reveals roles for RAB18 in eye development and organisation of the neuronal cytoskeleton. Dis Model Mech. 2014;7:711-22 pubmed publisher
  20. Ouyang Q, Lizarraga S, Schmidt M, Yang U, Gong J, Ellisor D, et al. Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development. Neuron. 2013;80:97-112 pubmed publisher
    ..Finally, exogenous BDNF rescues defects in neuronal arborization. We propose that NHE6 mutation leads to circuit defects that are in part due to impoverished neuronal arborization that may be treatable by enhanced TrkB signaling. ..
  21. Zhao C, Takita J, Tanaka Y, Setou M, Nakagawa T, Takeda S, et al. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell. 2001;105:587-97 pubmed
    ..We show that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene. This is clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy. ..
  22. Uesaka T, Nagashimada M, Enomoto H. Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System. J Neurosci. 2015;35:9879-88 pubmed publisher
    ..Cross-lineage differentiation capacity in SCPs suggests their potential involvement in the development and pathology of a wide variety of neural crest-derived cell types. ..
  23. Lazzell D, Belizaire R, Thakur P, Sherry D, Janz R. SV2B regulates synaptotagmin 1 by direct interaction. J Biol Chem. 2004;279:52124-31 pubmed publisher
    SV2 proteins are abundant synaptic vesicle proteins expressed in two major (SV2A and SV2B) and one minor (SV2C) isoform. SV2A and SV2B have been shown to be involved in the regulation of synaptic vesicle exocytosis...
  24. Audouard E, Schakman O, Rene F, Huettl R, Huber A, Loeffler J, et al. The Onecut transcription factor HNF-6 regulates in motor neurons the formation of the neuromuscular junctions. PLoS ONE. 2012;7:e50509 pubmed publisher
    ..Thus, HNF-6 controls in spinal motor neurons a genetic program that coordinates the formation of hindlimb neuromuscular junctions. ..
  25. Fukami S, Watanabe K, Iwata N, Haraoka J, Lu B, Gerard N, et al. Abeta-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology. Neurosci Res. 2002;43:39-56 pubmed
  26. An M, Lin W, Yang J, Dominguez B, Padgett D, Sugiura Y, et al. Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proc Natl Acad Sci U S A. 2010;107:10702-7 pubmed publisher
    ..Together, these data suggest that ACh negatively regulates axon growth and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms. ..
  27. Rich K, Zhan Y, Blanks J. Migration and synaptogenesis of cone photoreceptors in the developing mouse retina. J Comp Neurol. 1997;388:47-63 pubmed
    ..The types of cues used by maturing cone cells for their eventual sclerad location remain to be elucidated. ..
  28. Piccoli G, Condliffe S, Bauer M, Giesert F, Boldt K, De Astis S, et al. LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. J Neurosci. 2011;31:2225-37 pubmed publisher
    ..Our results suggest that LRRK2 modulates synaptic vesicle trafficking and distribution in neurons and in consequence participates in regulating the dynamics between vesicle pools inside the presynaptic bouton...
  29. Ferguson R, Serafeimidou Pouliou E, Subramanian V. Dynamic expression of the mouse orthologue of the human amyotropic lateral sclerosis associated gene C9orf72 during central nervous system development and neuronal differentiation. J Anat. 2016;229:871-891 pubmed publisher
    ..Our findings have implications for interpreting the pathophysiology caused by the repeat expansions in C9orf72 in mouse models. ..
  30. Prince J, Brignall A, Cutforth T, Shen K, Cloutier J. Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression. Development. 2013;140:2398-408 pubmed publisher
    ..Taken together, our results indicate that differential expression of Kirrels on vomeronasal axons generates a molecular code that dictates their proper coalescence into glomeruli within the AOB. ..
  31. Ahnert Hilger G, Kutay U, Chahoud I, Rapoport T, Wiedenmann B. Synaptobrevin is essential for secretion but not for the development of synaptic processes. Eur J Cell Biol. 1996;70:1-11 pubmed
    ..We conclude that synaptobrevin represents a marker for early events in synaptogenesis. Its proteolysis by tetanus toxin, however, does not interfere with the formation of synaptic contacts and neuronal differentiation. ..
  32. Moores T, Hasdemir B, Vega Riveroll L, Deuchars J, Parson S. Properties of presynaptic P2X7-like receptors at the neuromuscular junction. Brain Res. 2005;1034:40-50 pubmed
    ..We conclude that a P2X7-like receptor is present at mouse motor nerve terminals, and that their activation promotes vesicle release. ..
  33. Belizaire R, Komanduri C, Wooten K, Chen M, Thaller C, Janz R. Characterization of synaptogyrin 3 as a new synaptic vesicle protein. J Comp Neurol. 2004;470:266-81 pubmed
    ..Altogether, our data indicate that neuronal synaptogyrins are differentially expressed protein isoforms that may represent functionally distinct populations of synapses and/or synaptic vesicles. ..
  34. Pellet J, Haefliger J, Staple J, Widmann C, Welker E, Hirling H, et al. Spatial, temporal and subcellular localization of islet-brain 1 (IB1), a homologue of JIP-1, in mouse brain. Eur J Neurosci. 2000;12:621-32 pubmed
  35. Kwon S, Chapman E. Glycosylation is dispensable for sorting of synaptotagmin 1 but is critical for targeting of SV2 and synaptophysin to recycling synaptic vesicles. J Biol Chem. 2012;287:35658-68 pubmed publisher
    ..In this study, we analyzed all glycosylation sites on synaptotagmin 1, synaptophysin, and SV2A via mutagenesis and optical imaging of pHluorin-tagged proteins in cultured neurons from knock-out mice lacking ..
  36. Herbst R, Avetisova E, Burden S. Restoration of synapse formation in Musk mutant mice expressing a Musk/Trk chimeric receptor. Development. 2002;129:5449-60 pubmed
    ..Moreover, acetylcholine receptor clustering and motor terminal branching are restored in parallel, indicating that the extent of presynaptic differentiation is matched to the extent of postsynaptic differentiation. ..
  37. Chakkalakal J, Nishimune H, Ruas J, Spiegelman B, Sanes J. Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons. Development. 2010;137:3489-99 pubmed publisher
    ..Here we show in mice that the synaptic vesicle protein SV2A is selectively localized in motor nerve terminals on slow (type I and small type IIA) muscle fibers; its close ..
  38. Lamberty Y, Detrait E, Leclercq K, Michel A, De Ryck M. Behavioural phenotyping reveals anxiety-like features of SV2A deficient mice. Behav Brain Res. 2009;198:329-33 pubmed publisher
    b>Synaptic vesicle protein 2A (SV2A) is involved in neurotransmitter release and has been identified as the binding site for levetiracetam (Keppra), a novel antiepileptic drug. Homozygous SV2A (-/-) mice are not viable beyond a few weeks...
  39. Burgess R, Skarnes W, Sanes J. Agrin isoforms with distinct amino termini: differential expression, localization, and function. J Cell Biol. 2000;151:41-52 pubmed
    ..Thus, basal lamina-associated LN-agrin is required for neuromuscular synaptogenesis, whereas cell-associated SN-agrin may play distinct roles in the central nervous system. ..
  40. Vergaño Vera E, Yusta Boyo M, De Castro F, Bernad A, de Pablo F, Vicario Abejón C. Generation of GABAergic and dopaminergic interneurons from endogenous embryonic olfactory bulb precursor cells. Development. 2006;133:4367-79 pubmed
    ..These findings suggest that, in addition to receiving interneurons from the LGE, the embryonic OB contains molecularly distinct local precursor cells that generate mature GABAergic and dopaminergic neurons. ..
  41. Yao J, de la Iglesia H, Bajjalieh S. Loss of the SV2-like protein SVOP produces no apparent deficits in laboratory mice. PLoS ONE. 2013;8:e68215 pubmed publisher
    Neurons express two families of transporter-like proteins - Synaptic Vesicle protein 2 (SV2A, B, and C) and SV2-related proteins (SVOP and SVOPL)...
  42. Zhang N, Gordon S, Fritsch M, Esoof N, Campbell D, Gourlay R, et al. Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1. J Neurosci. 2015;35:2492-507 pubmed publisher
    b>Synaptic vesicle protein 2A (SV2A) is a ubiquitous component of synaptic vesicles (SVs). It has roles in both SV trafficking and neurotransmitter release...
  43. Apel E, Glass D, Moscoso L, Yancopoulos G, Sanes J. Rapsyn is required for MuSK signaling and recruits synaptic components to a MuSK-containing scaffold. Neuron. 1997;18:623-35 pubmed
    ..This signaling requires the kinase domain of MuSK, but not its ectodomain. Thus, MuSK may interact with rapsyn in multiple ways to play both structural and signaling roles in agrin-induced differentiation. ..
  44. Arnold M, Cross R, Singleton K, Zlatic S, Chapleau C, Mullin A, et al. The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin. Front Cell Neurosci. 2016;10:218 pubmed
    ..We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function. ..
  45. Sarria J, Catsicas S, Hornung J, Hirling H. Developmental and spatial expression pattern of syntaxin 13 in the mouse central nervous system. Cell Tissue Res. 2002;309:209-18 pubmed
    ..In conclusion, the developmentally regulated syntaxin 13 expression in various neuronal populations is consistent with its involvement in endocytic trafficking and neurite outgrowth. ..
  46. Pan J, Luk C, Kent G, Cutz E, Yeger H. Pulmonary neuroendocrine cells, airway innervation, and smooth muscle are altered in Cftr null mice. Am J Respir Cell Mol Biol. 2006;35:320-6 pubmed
    ..of PNEC/NEB, innervation and cell mass of airway smooth muscle, and neuromuscular junctions using synaptic vesicle protein 2, smooth muscle actin, and synaptophysin markers, respectively...
  47. Lynch B, Matagne A, Brännström A, von Euler A, Jansson M, Hauzenberger E, et al. Visualization of SV2A conformations in situ by the use of Protein Tomography. Biochem Biophys Res Commun. 2008;375:491-5 pubmed publisher
    The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography...
  48. Ventruti A, Kazdoba T, Niu S, D ARCANGELO G. Reelin deficiency causes specific defects in the molecular composition of the synapses in the adult brain. Neuroscience. 2011;189:32-42 pubmed publisher
    ..These studies may provide insights into the etiology of cognitive disorders associated with deficiencies in Reelin signaling and PTEN dysfunction. ..
  49. Hanson M, Fregoso V, Vrana J, Tucker C, Niswander L. Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders. Dev Biol. 2014;395:84-95 pubmed publisher
    ..Our findings identify PEX10 function, and likely other PEX proteins, as an essential component of the spinal locomotor circuit. ..
  50. Terrado J, Burgess R, DeChiara T, Yancopoulos G, Sanes J, Kato A. Motoneuron survival is enhanced in the absence of neuromuscular junction formation in embryos. J Neurosci. 2001;21:3144-50 pubmed
    ..The motoneuron numbers in the double mutants parallel those of the single MuSK-deficient mice, indicating that synapse disruption can even overcome the deleterious effect of CNTFRalpha ablation. ..
  51. Medrihan L, Rohlmann A, Fairless R, Andrae J, Döring M, Missler M, et al. Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses. J Physiol. 2009;587:5095-106 pubmed publisher
  52. Yeh F, Dong M, Yao J, Tepp W, Lin G, Johnson E, et al. SV2 mediates entry of tetanus neurotoxin into central neurons. PLoS Pathog. 2010;6:e1001207 pubmed publisher
    ..Toxin entry into knockout neurons was rescued by infecting with viruses that express SV2A or SV2B...