// Workers AI · dad joke modeWhat did SV2A say to its friend? "You're a valve-uable buddy
| SV2A | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | SV2A, SV2, synaptic vesicle glycoprotein 2A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 185860; MGI: 1927139; HomoloGene: 32237; GeneCards: SV2A; OMA:SV2A - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein belonging to a family of keratan sulfate proteoglycans, located on the synaptic vesicles of mammalian neuronal and endocrine cells. It is encoded by the SV2A gene.[5][6][7]
SV2A is the most widely expressed isoform of the SV2 family (which also includes the SV2B and SV2C proteins) found in all brain regions.[8] The role of the SV2 proteins is not well understood; however, they are thought to be involved in regulating vesicular processes.[8]
The SV2A protein is a target of the anti-epileptic drugs (anticonvulsants) levetiracetam and brivaracetam[9] but it is not clear how these drug affect SV2A activity.[10]
Localisation
[edit]SV2A is differentially expressed in both inhibitory GABAergic and excitatory glutamatergic terminals[11] however it is not expressed in all synapses[12] as was previously thought.[13] There is a slightly stronger colocalisation between SV2A and GABA than glutamate[11] and the association differs across brain regions and changes with developmental stages.[14]
SV2A PET
[edit]Several PET radiotracers targeting SV2A have been developed, allowing for measuring SV2A density in-vivo: [11C]LEV, [11C]UCB-A, [11C]-UCB-H, [18F]UCB-J, [18F]Syn-VesT-1, [18F]Syn-VesT-2, and [18F]SDM-16. SV2A density has been used as a proxy for measuring in vivo synaptic density.[15][16][17][18] A 2024 systematic review and meta-analysis of [11C]UCB-J PET studies reported lower SV2A binding in individuals with psychotic disorders compared with healthy controls.[19]
See also
[edit]References
[edit]- 1 2 3 GRCh38: Ensembl release 89: ENSG00000159164 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038486 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Bajjalieh SM, Peterson K, Linial M, Scheller RH (March 1993). "Brain contains two forms of synaptic vesicle protein 2". Proceedings of the National Academy of Sciences of the United States of America. 90 (6): 2150–2154. Bibcode:1993PNAS...90.2150B. doi:10.1073/pnas.90.6.2150. PMC 46043. PMID 7681585.
- ↑ Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, et al. (December 1999). "Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A)". Proceedings of the National Academy of Sciences of the United States of America. 96 (26): 15268–15273. Bibcode:1999PNAS...9615268C. doi:10.1073/pnas.96.26.15268. PMC 24809. PMID 10611374.
- ↑ "Entrez Gene: SV2A synaptic vesicle glycoprotein 2A".
- 1 2 Rossi R, Arjmand S, Bærentzen SL, Gjedde A, Landau AM (2022). "Synaptic Vesicle Glycoprotein 2A: Features and Functions". Frontiers in Neuroscience. 16 864514. doi:10.3389/fnins.2022.864514. PMC 9096842. PMID 35573314.
- ↑ Ulloa CM, Towfigh A, Safdieh J (2009). "Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures". Neuropsychiatric Disease and Treatment. 5: 467–476. doi:10.2147/ndt.s4844. PMC 2747386. PMID 19777068.
- ↑ Contreras-García IJ, Cárdenas-Rodríguez N, Romo-Mancillas A, Bandala C, Zamudio SR, Gómez-Manzo S, et al. (April 2022). "Levetiracetam Mechanisms of Action: From Molecules to Systems". Pharmaceuticals. 15 (4). Basel, Switzerland: 475. doi:10.3390/ph15040475. PMC 9030752. PMID 35455472.
- 1 2 Mendoza-Torreblanca JG, García-Cruz ME, Sánchez-Cruz I, Gomez-Gonzalez B, Juárez-Méndez S, Gómez-Lira G (November 2019). "Analysis of Differential Expression of Synaptic Vesicle Protein 2A in the Adult Rat Brain". Neuroscience. 419: 108–120. doi:10.1016/j.neuroscience.2019.09.004. PMID 31520710.
- ↑ Wong T, Qiu Z, Notman B, Tavares A, Smith C, Grant SG (2025). "SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies". Wellcome Open Research. 10: 415. bioRxiv 10.1101/2024.07.15.603608. doi:10.12688/wellcomeopenres.24668.1. PMC 12603525. PMID 41229902.
- ↑ Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH (September 1994). "Differential expression of synaptic vesicle protein 2 (SV2) isoforms". The Journal of Neuroscience. 14 (9): 5223–5235. doi:10.1523/JNEUROSCI.14-09-05223.1994. PMC 6577109. PMID 8083732.
- ↑ Vanoye-Carlo A, Gómez-Lira G (July 2019). "Differential expression of SV2A in hippocampal glutamatergic and GABAergic terminals during postnatal development". Brain Research. 1715: 73–83. doi:10.1016/j.brainres.2019.03.021. PMID 30905653.
- ↑ Onwordi EC, Halff EF, Whitehurst T, Mansur A, Cotel MC, Wells L, et al. (January 2020). "Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats". Nature Communications. 11 (1) 246. Bibcode:2020NatCo..11..246O. doi:10.1038/s41467-019-14122-0. PMC 6959348. PMID 31937764.
- ↑ Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, et al. (December 2021). "In vivo evidence of lower synaptic vesicle density in schizophrenia". Molecular Psychiatry. 26 (12): 7690–7698. doi:10.1038/s41380-021-01184-0. PMID 34135473.
- ↑ Yoon JH, Zhang Z, Mormino E, Davidzon G, Minzenberg MJ, Ballon J, et al. (May 2023). "Reductions in synaptic marker SV2A in early-course Schizophrenia". Journal of Psychiatric Research. 161: 213–217. doi:10.1016/j.jpsychires.2023.02.026. PMID 36934603.
- ↑ Holmes SE, Abdallah C, Esterlis I (January 2023). "Imaging synaptic density in depression". Neuropsychopharmacology. 48 (1): 186–190. doi:10.1038/s41386-022-01368-4. PMC 9700860. PMID 35768568.
- ↑ Husain MO, Jones B, Arshad U, Ameis SH, Mirfallah G, Schifani C, et al. (June 2024). "A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders". BMC Psychiatry. 24 (1) 460. doi:10.1186/s12888-024-05788-y. PMC 11188231. PMID 38898401.
Further reading
[edit]- Bajjalieh SM, Peterson K, Shinghal R, Scheller RH (August 1992). "SV2, a brain synaptic vesicle protein homologous to bacterial transporters". Science. 257 (5074). New York, N.Y.: 1271–1273. Bibcode:1992Sci...257.1271B. doi:10.1126/science.1519064. PMID 1519064.
- Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, et al. (October 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–286. doi:10.1093/dnares/5.5.277. PMID 9872452.
- Son YJ, Scranton TW, Sunderland WJ, Baek SJ, Miner JH, Sanes JR, et al. (January 2000). "The synaptic vesicle protein SV2 is complexed with an alpha5-containing laminin on the nerve terminal surface". The Journal of Biological Chemistry. 275 (1): 451–460. doi:10.1074/jbc.275.1.451. PMID 10617638.
- Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–292. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, et al. (June 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. 101 (26): 9861–9866. Bibcode:2004PNAS..101.9861L. doi:10.1073/pnas.0308208101. PMC 470764. PMID 15210974.
- Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
- DeGiorgis JA, Jaffe H, Moreira JE, Carlotti CG, Leite JP, Pant HC, et al. (2005). "Phosphoproteomic analysis of synaptosomes from human cerebral cortex". Journal of Proteome Research. 4 (2): 306–315. doi:10.1021/pr0498436. PMID 15822905.
- Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–126. doi:10.1093/dnares/12.2.117. PMID 16303743.
- Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.