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
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSV2A, SV2, synaptic vesicle glycoprotein 2A
External IDsOMIM: 185860; MGI: 1927139; HomoloGene: 32237; GeneCards: SV2A; OMA:SV2A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_014849
NM_001278719
NM_001328674
NM_001328675

NM_022030

RefSeq (protein)

NP_001265648
NP_001315603
NP_001315604
NP_055664

NP_071313

Location (UCSC)Chr 1: 149.9 – 149.92 MbChr 3: 96.09 – 96.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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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]

SV2A PET

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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]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000159164Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038486Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. Bibcode:1993PNAS...90.2150B. doi:10.1073/pnas.90.6.2150. PMC 46043. PMID 7681585.
  6. ^ 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.
  7. ^ "Entrez Gene: SV2A synaptic vesicle glycoprotein 2A".
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.

Further reading

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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.