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]
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 GABA ergic 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]
^ a b c GRCh38: Ensembl release 89: ENSG00000159164 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038486 – Ensembl , May 2017
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^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
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^ 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. Bibcode :1999PNAS...9615268C . doi :10.1073/pnas.96.26.15268 . PMC 24809 . PMID 10611374 .
^ "Entrez Gene: SV2A synaptic vesicle glycoprotein 2A" .
^ a b 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. doi :10.3389/fnins.2022.864514 . ISSN 1662-4548 . 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 : 467–76. doi :10.2147/ndt.s4844 . PMC 2747386 . PMID 19777068 .
^ 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 . 15 (4): 475. doi :10.3390/ph15040475 . ISSN 1424-8247 . PMC 9030752 . PMID 35455472 .
^ 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 . 419 : 108–120. doi :10.1016/j.neuroscience.2019.09.004 . PMID 31520710 .
^ Wong, Theresa; Qiu, Zhen; Notman, Beverly; Tavares, Adriana; Smith, Colin; Grant, Seth G. N. (2024-07-18), SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies , doi :10.1101/2024.07.15.603608 , retrieved 2024-10-02
^ 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 . 14 (9): 5223–5235. doi :10.1523/JNEUROSCI.14-09-05223.1994 . ISSN 0270-6474 . PMC 6577109 . PMID 8083732 .
^ 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 . 419 : 108–120. doi :10.1016/j.neuroscience.2019.09.004 . PMID 31520710 .
^ Vanoye-Carlo, América; Gómez-Lira, Gisela (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, 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 .
^ Holmes, Sophie E.; Abdallah, Chadi; Esterlis, Irina (January 2023). "Imaging synaptic density in depression" . Neuropsychopharmacology . 48 (1): 186–190. doi :10.1038/s41386-022-01368-4 . ISSN 0893-133X . PMC 9700860 . PMID 35768568 .
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Overview of all the structural information available in the PDB for UniProt : Q7L0J3 (Synaptic vesicle glycoprotein 2A) at the PDBe-KB .