SV2A explained

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's encoded by the SV2A gene.^{[1] [2] [3]}

SV2A is the most widely expressed isoform of the SV2 family (which also includes the SV2B and SV2C proteins) found in all brain regions.^[4] The role of the SV2 proteins is not well understood, however they are thought to be involved in regulating vesicular processes.

The SV2A protein is a target of the anti-epileptic drugs (anticonvulsants) levetiracetam and brivaracetam^[5] but it is not clear how these drug affect SV2A activity.^[6]

Localisation

SV2A is differentially expressed in both inhibitory GABAergic and excitatory glutamatergic terminals^[7] however it is not expressed in all synapses as was previously thought.^[8] There is a slightly stronger colocalisation between SV2A and GABA than glutamate^[9] and the association differs across brain regions and changes with developmental stages.^[10]

SV2A PET

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.^{[11] [12] [13] [14]}

See also

• SV2B

Further reading

• Bajjalieh SM, Peterson K, Shinghal R, Scheller RH . SV2, a brain synaptic vesicle protein homologous to bacterial transporters . Science . 257 . 5074 . 1271–3 . Aug 1992 . 1519064 . 10.1126/science.1519064 . 1992Sci...257.1271B .
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . 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 . 277–86 . Oct 1998 . 9872452 . 10.1093/dnares/5.5.277 . free .
• Son YJ, Scranton TW, Sunderland WJ, Baek SJ, Miner JH, Sanes JR, Carlson SS . The synaptic vesicle protein SV2 is complexed with an alpha5-containing laminin on the nerve terminal surface . The Journal of Biological Chemistry . 275 . 1 . 451–60 . Jan 2000 . 10617638 . 10.1074/jbc.275.1.451 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . Nov 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . Mar 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Reports . 1 . 3 . 287–92 . Sep 2000 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .
• Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B . 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 . 9861–6 . Jun 2004 . 15210974 . 470764 . 10.1073/pnas.0308208101 . 2004PNAS..101.9861L . free .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . Oct 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• DeGiorgis JA, Jaffe H, Moreira JE, Carlotti CG, Leite JP, Pant HC, Dosemeci A . Phosphoproteomic analysis of synaptosomes from human cerebral cortex . Journal of Proteome Research . 4 . 2 . 306–15 . 2005 . 15822905 . 10.1021/pr0498436 .
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T . 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 . 117–26 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . free .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . The LIFEdb database in 2006 . Nucleic Acids Research . 34 . Database issue . D415–8 . Jan 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .

Notes and References

1. Bajjalieh SM, Peterson K, Linial M, Scheller RH . Mar 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 . 2150–4 . 1993PNAS...90.2150B . 10.1073/pnas.90.6.2150 . 46043 . 7681585 . free.
2. Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, Scheller RH, Chavkin C, Bajjalieh SM . Dec 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 . 15268–73 . 1999PNAS...9615268C . 10.1073/pnas.96.26.15268 . 24809 . 10611374 . free.
3. Web site: Entrez Gene: SV2A synaptic vesicle glycoprotein 2A .
4. Rossi . Rachele . Arjmand . Shokouh . Bærentzen . Simone Larsen . Gjedde . Albert . Landau . Anne M. . 2022-04-28 . Synaptic Vesicle Glycoprotein 2A: Features and Functions . Frontiers in Neuroscience . 16 . 864514 . 10.3389/fnins.2022.864514 . 1662-4548 . 9096842 . 35573314 . free.
5. Ulloa CM, Towfigh A, Safdieh J . Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures . Neuropsychiatric Disease and Treatment . 5 . 467–76 . 2009 . 19777068 . 2747386 . 10.2147/ndt.s4844 . free .
6. Contreras-García . Itzel Jatziri . Cárdenas-Rodríguez . Noemí . Romo-Mancillas . Antonio . Bandala . Cindy . Zamudio . Sergio R. . Gómez-Manzo . Saúl . Hernández-Ochoa . Beatriz . Mendoza-Torreblanca . Julieta Griselda . Pichardo-Macías . Luz Adriana . 2022-04-13 . Levetiracetam Mechanisms of Action: From Molecules to Systems . Pharmaceuticals . en . 15 . 4 . 475 . 10.3390/ph15040475 . free . 1424-8247 . 9030752 . 35455472.
7. Mendoza-Torreblanca . Julieta G. . García-Cruz . M. Edna . Sánchez-Cruz . Itzel . Gomez-Gonzalez . Beatriz . Juárez-Méndez . Sergio . Gómez-Lira . Gisela . November 2019 . Analysis of Differential Expression of Synaptic Vesicle Protein 2A in the Adult Rat Brain . Neuroscience . en . 419 . 108–120 . 10.1016/j.neuroscience.2019.09.004. 31520710 .
8. Bajjalieh . S. M. . Frantz . G. D. . Weimann . J. M. . McConnell . S. K. . Scheller . R. H. . 1994-09-01 . Differential expression of synaptic vesicle protein 2 (SV2) isoforms . Journal of Neuroscience . en . 14 . 9 . 5223–5235 . 10.1523/JNEUROSCI.14-09-05223.1994 . 0270-6474 . 8083732. 6577109 .
9. Mendoza-Torreblanca . Julieta G. . García-Cruz . M. Edna . Sánchez-Cruz . Itzel . Gomez-Gonzalez . Beatriz . Juárez-Méndez . Sergio . Gómez-Lira . Gisela . November 2019 . Analysis of Differential Expression of Synaptic Vesicle Protein 2A in the Adult Rat Brain . Neuroscience . en . 419 . 108–120 . 10.1016/j.neuroscience.2019.09.004. 31520710 .
10. Vanoye-Carlo . América . Gómez-Lira . Gisela . July 2019 . Differential expression of SV2A in hippocampal glutamatergic and GABAergic terminals during postnatal development . Brain Research . en . 1715 . 73–83 . 10.1016/j.brainres.2019.03.021. 30905653 .
11. Onwordi . Ellis Chika . Halff . Els F. . Whitehurst . Thomas . Mansur . Ayla . Cotel . Marie-Caroline . Wells . Lisa . Creeney . Hannah . Bonsall . David . Rogdaki . Maria . Shatalina . Ekaterina . Reis Marques . Tiago . Rabiner . Eugenii A. . Gunn . Roger N. . Natesan . Sridhar . Vernon . Anthony C. . 2020-01-14 . Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats . Nature Communications . en . 11 . 1 . 246 . 10.1038/s41467-019-14122-0 . 2041-1723 . 6959348 . 31937764. 2020NatCo..11..246O .
12. Radhakrishnan . Rajiv . Skosnik . Patrick D. . Ranganathan . Mohini . Naganawa . Mika . Toyonaga . Takuya . Finnema . Sjoerd . Hillmer . Ansel T. . Esterlis . Irina . Huang . Yiyun . Nabulsi . Nabeel . Carson . Richard E. . D’Souza . Deepak C. . December 2021 . In vivo evidence of lower synaptic vesicle density in schizophrenia . Molecular Psychiatry . en . 26 . 12 . 7690–7698 . 10.1038/s41380-021-01184-0 . 34135473 . 1359-4184.
13. Yoon . Jong H. . Zhang . Zhener . Mormino . Elizabeth . Davidzon . Guido . Minzenberg . Michael J. . Ballon . Jacob . Kalinowski . Agnieszka . Hardy . Kate . Naganawa . Mika . Carson . Richard E. . Khalighi . Mehdi . Park . Jun Hyung . Levinson . Douglas F. . Chin . Frederick T. . May 2023 . Reductions in synaptic marker SV2A in early-course Schizophrenia . Journal of Psychiatric Research . en . 161 . 213–217 . 10.1016/j.jpsychires.2023.02.026. 36934603 .
14. Holmes . Sophie E. . Abdallah . Chadi . Esterlis . Irina . January 2023 . Imaging synaptic density in depression . Neuropsychopharmacology . en . 48 . 1 . 186–190 . 10.1038/s41386-022-01368-4 . 0893-133X . 9700860 . 35768568.