Vesicular monoamine transporter 2
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Location (UCSC) | Chr 10: 117.24 – 117.28 Mb | Chr 19: 59.25 – 59.28 Mb | |||||||
PubMed search | [3] | [4] |
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The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a
Binding sites and ligands
SLC18A2 is believed to possess at least two distinct binding sites, which are characterized by
Researchers have found that inhibiting the dopamine transporter (but not SLC18A2) will block the effects of amphetamine and cocaine; while, in another experiment, observing that disabling SLC18A2 (but not the dopamine transporter) prevents any notable action in test animals after amphetamine administration yet not cocaine administration. This suggests that amphetamine may be an atypical substrate with little to no ability to prevent dopamine reuptake via binding to the dopamine transporter but, instead, uses it to enter a neuron where it then interacts with SLC18A2 to induce efflux of dopamine from their vesicles into the cytoplasm whereupon dopamine transporters with amphetamine substrates attached move this recently liberated dopamine into the synaptic cleft.[10]
Inhibition
SLC18A2 is essential for enabling the release of neurotransmitters from the axon terminals of monoamine neurons into the synaptic cleft. If SLC18A2 function is inhibited or compromised, monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms (i.e., exocytosis resulting from action potentials).
In popular culture
Geneticist Dean Hamer has suggested that a particular allele of the SLC18A2 gene correlates with spirituality using data from a smoking survey, which included questions intended to measure "self-transcendence". Hamer performed the spirituality study on the side, independently of the National Cancer Institute smoking study. His findings were published in the mass-market book The God Gene: How Faith Is Hard-Wired into Our Genes.[12][13] Hamer himself notes that SLC18A2 plays at most a minor role in influencing spirituality.[14] Furthermore, Hamer's claim that the SLC18A2 gene contributes to spirituality is controversial.[14] Hamer's study has not been published in a peer-reviewed journal and a reanalysis of the correlation demonstrates that it is not statistically significant.[14][15]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000165646 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025094 - 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.
- S2CID 8062412.
- S2CID 20764857.
- PMID 23034651.
- ^ S2CID 2359509.
They also demonstrated competition for binding between METH and reserpine, suggesting they might bind to the same site on VMAT. George Uhl's laboratory similarly reported that AMPH displaced the VMAT2 blocker tetrabenazine (Gonzalez et al., 1994). Tetrabenazine and reserpine are thought to bind to different sites on VMAT (Schuldiner et al., 1993a)
- PMID 22638813.
- PMID 26879809.
- PMID 12505801.
- ISBN 0-385-50058-0.
- ^ Kluger J, Chu J, Liston B, Sieger M, Williams D (25 October 2004). "Is God in our genes?". TIME. Time Inc. Archived from the original on 30 September 2007. Retrieved 8 April 2007.
- ^ PMID 18316816.
- .
Further reading
- Need AC, Keefe RS, Ge D, Grossman I, Dickson S, McEvoy JP, Goldstein DB (2009). "Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis". Eur. J. Hum. Genet. 17 (7): 946–57. PMID 19156168.
- Okamura N, Villemagne VL, Drago J, Pejoska S, Dhamija RK, Mulligan RS, Ellis JR, Ackermann U, O'Keefe G, Jones G, Kung HF, Pontecorvo MJ, Skovronsky D, Rowe CC (2010). "In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with (18)F-AV-133". J. Nucl. Med. 51 (2): 223–8. PMID 20080893.
- Saisho Y, Harris PE, Butler AE, Galasso R, Gurlo T, Rizza RA, Butler PC (2008). "Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas". J. Mol. Histol. 39 (5): 543–51. PMID 18791800.
- Tsolakis AV, Grimelius L, Stridsberg M, Falkmer SE, Waldum HL, Saras J, Janson ET (2009). "Obestatin/ghrelin cells in normal mucosa and endocrine tumours of the stomach". Eur. J. Endocrinol. 160 (6): 941–9. PMID 19289536.
- Harris PE, Ferrara C, Barba P, Polito T, Freeby M, Maffei A (2008). "VMAT2 gene expression and function as it applies to imaging beta-cell mass". J. Mol. Med. 86 (1): 5–16. S2CID 20374043.
- Roe BE, Tilley MR, Gu HH, Beversdorf DQ, Sadee W, Haab TC, Papp AC (2009). "Financial and psychological risk attitudes associated with two single nucleotide polymorphisms in the nicotine receptor (CHRNA4) gene". PLOS ONE. 4 (8): e6704. PMID 19693267.
- Sørensen KD, Wild PJ, Mortezavi A, Adolf K, Tørring N, Heebøll S, Ulhøi BP, Ottosen P, Sulser T, Hermanns T, Moch H, Borre M, Ørntoft TF, Dyrskjøt L (2009). "Genetic and epigenetic SLC18A2 silencing in prostate cancer is an independent adverse predictor of biochemical recurrence after radical prostatectomy". Clin. Cancer Res. 15 (4): 1400–10. PMID 19228741.
- Watabe M, Nakaki T (2008). "Mitochondrial complex I inhibitor rotenone inhibits and redistributes vesicular monoamine transporter 2 via nitration in human dopaminergic SH-SY5Y cells". Mol. Pharmacol. 74 (4): 933–40. S2CID 1844073.
- Catlow K, Ashurst HL, Varro A, Dimaline R (2007). "Identification of a gastrin response element in the vesicular monoamine transporter type 2 promoter and requirement of 20 S proteasome subunits for transcriptional activity". J. Biol. Chem. 282 (23): 17069–77. PMID 17442673.
- Yosifova A, Mushiroda T, Stoianov D, Vazharova R, Dimova I, Karachanak S, Zaharieva I, Milanova V, Madjirova N, Gerdjikov I, Tolev T, Velkova S, Kirov G, Owen MJ, O'Donovan MC, Toncheva D, Nakamura Y (2009). "Case-control association study of 65 candidate genes revealed a possible association of a SNP of HTR5A to be a factor susceptible to bipolar disease in Bulgarian population". J Affect Disord. 117 (1–2): 87–97. PMID 19328558.
- Tabakoff B, Saba L, Printz M, Flodman P, Hodgkinson C, Goldman D, Koob G, Richardson HN, Kechris K, Bell RL, Hübner N, Heinig M, Pravenec M, Mangion J, Legault L, Dongier M, Conigrave KM, Whitfield JB, Saunders J, Grant B, Hoffman PL (2009). "Genetical genomic determinants of alcohol consumption in rats and humans". BMC Biol. 7: 70. PMID 19874574.
- Zheng G, Dwoskin LP, Crooks PA (2006). "Vesicular monoamine transporter 2: role as a novel target for drug development". AAPS J. 8 (4): E682-92. PMID 17233532.
- Crowley JJ, Lipsky RH, Lucki I, Berrettini WH (2008). "Variation in the genes encoding vesicular monoamine transporter 2 and beta-1 adrenergic receptor and antidepressant treatment outcome". Psychiatr. Genet. 18 (5): 248–51. S2CID 206148319.
- Guo JT, Chen AQ, Kong Q, Zhu H, Ma CM, Qin C (2008). "Inhibition of vesicular monoamine transporter-2 activity in alpha-synuclein stably transfected SH-SY5Y cells". Cell. Mol. Neurobiol. 28 (1): 35–47. S2CID 20230170.
- Talkowski ME, Kirov G, Bamne M, Georgieva L, Torres G, Mansour H, Chowdari KV, Milanova V, Wood J, McClain L, Prasad K, Shirts B, Zhang J, O'Donovan MC, Owen MJ, Devlin B, Nimgaonkar VL (2008). "A network of dopaminergic gene variations implicated as risk factors for schizophrenia". Hum. Mol. Genet. 17 (5): 747–58. PMID 18045777.
- Verney C, Lebrand C, Gaspar P (2002). "Changing distribution of monoaminergic markers in the developing human cerebral cortex with special emphasis on the serotonin transporter". Anat. Rec. 267 (2): 87–93. S2CID 2088307.
- Perlis RH, Moorjani P, Fagerness J, Purcell S, Trivedi MH, Fava M, Rush AJ, Smoller JW (2008). "Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study". Neuropsychopharmacology. 33 (12): 2810–9. PMID 18288090.
- Caudle WM, Richardson JR, Wang MZ, Taylor TN, Guillot TS, McCormack AL, Colebrooke RE, Di Monte DA, Emson PC, Miller GW (2007). "Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration". J. Neurosci. 27 (30): 8138–48. PMID 17652604.
External links
- Vesicular+Monoamine+Transporter+2 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)