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.[5][6][7]
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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]
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[14] and the association differs across brain regions and changes with developmental stages.[15]
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.[16][17][18][19]
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. 11 (1): 246. Bibcode:2020NatCo..11..246O. doi:10.1038/s41467-019-14122-0. ISSN 2041-1723. PMC 6959348. PMID 31937764. 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. 26 (12): 7690–7698. doi:10.1038/s41380-021-01184-0. ISSN 1359-4184. PMID 34135473. 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. 161: 213–217. doi:10.1016/j.jpsychires.2023.02.026. PMID 36934603.
- Bajjalieh SM, Peterson K, Shinghal R, Scheller RH (Aug 1992). "SV2, a brain synaptic vesicle protein homologous to bacterial transporters". Science. 257 (5074): 1271–3. Bibcode:1992Sci...257.1271B. doi:10.1126/science.1519064. PMID 1519064.
- Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Oct 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): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
- Son YJ, Scranton TW, Sunderland WJ, Baek SJ, Miner JH, Sanes JR, Carlson SS (Jan 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): 451–60. doi:10.1074/jbc.275.1.451. PMID 10617638.
- Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- 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 (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B (Jun 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): 9861–6. 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, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
- DeGiorgis JA, Jaffe H, Moreira JE, Carlotti CG, Leite JP, Pant HC, Dosemeci A (2005). "Phosphoproteomic analysis of synaptosomes from human cerebral cortex". Journal of Proteome Research. 4 (2): 306–15. doi:10.1021/pr0498436. PMID 15822905.
- 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 (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): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
- 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 (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
- Overview of all the structural information available in the PDB for UniProt: Q7L0J3 (Synaptic vesicle glycoprotein 2A) at the PDBe-KB.
