GABA transporter 1

SLC6A1
Identifiers
Aliases SLC6A1, GABATHG, GABATR, GAT1, MAE, GABA transporter 1, solute carrier family 6 member 1
External IDs MGI: 95627 HomoloGene: 2290 GeneCards: SLC6A1
Genetically Related Diseases
Conduct disorder[1]
Targeted by Drug
ci-966 free base, SKF89976A, tiagabine[2]
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

6529

232333

Ensembl

ENSG00000157103

ENSMUSG00000030310

UniProt

P30531

P31648

RefSeq (mRNA)

NM_003042

NM_178703

RefSeq (protein)

NP_003033.3

NP_848818.1

Location (UCSC) Chr 3: 10.99 – 11.04 Mb Chr 6: 114.28 – 114.32 Mb
PubMed search [3] [4]
Wikidata
View/Edit HumanView/Edit Mouse

GABA transporter 1 (GAT1) also known as sodium- and chloride-dependent GABA transporter 1 is a protein that in humans is encoded by the SLC6A1 gene.[5][6]

Function

GAT1 a gamma-aminobutyric acid (GABA) transporter, which removes GABA from the synaptic cleft.[7] GABA Transporter 1 uses Na+ and Cl- to create a gradient, which removes or adds GABA to extracellular spaces in the cerebrum and cerebellum. The stoichiometry for GABA Transporter 1 is 2 Na+: 1 Cl-: 1 GABA. The activity of GAT1 is largely dependent on the presence of Na+, while Cl- assists by increasing the ability for GAT-1 to uptake GABA.[8]

Diseases

Research recorded in The American Journal of Psychiatry has shown that schizophrenia patients have GABA synthesis and expression altered, leading to the conclusion that GABA Transporter-1, which adds and removes GABA from the synaptic cleft, plays a role in the development of neurological disorders such as Schizophrenia.[9]

Interactions

SLC6A1 has been shown to interact with STX1A.[10][11][12]

See also

References

  1. ↑ "Diseases that are genetically associated with SLC6A1 view/edit references on wikidata".
  2. ↑ "Drugs that physically interact with Sodium- and chloride-dependent GABA transporter 1 view/edit references on wikidata".
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ Huang F, Shi LJ, Heng HH, Fei J, Guo LH (September 1995). "Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24-p25". Genomics. 29 (1): 302–4. doi:10.1006/geno.1995.1253. PMID 8530094.
  6. ↑ "Entrez Gene: SLC6A1 solute carrier family 6 (neurotransmitter transporter, GABA), member 1".
  7. ↑ Hirunsatit R, George ED, Lipska BK, Elwafi HM, Sander L, Yrigollen CM, Gelernter J, Grigorenko EL, Lappalainen J, Mane S, Nairn AC, Kleinman JE, Simen AA (January 2009). "Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity". Pharmacogenetics and Genomics. 19 (1): 53–65. doi:10.1097/FPC.0b013e328318b21a. PMC 2791799Freely accessible. PMID 19077666.
  8. ↑ Jin XT, Galvan A, Wichmann T, Smith Y (28 July 2011). "Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia". Frontiers in Systems Neuroscience. 5: 63. doi:10.3389/fnsys.2011.00063. PMID 21847373.
  9. ↑ Volk D, Austin M, Pierri J, Sampson A, Lewis D (February 2001). "GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons". The American Journal of Psychiatry. 158 (2): 256–65. doi:10.1176/appi.ajp.158.2.256. PMID 11156808.
  10. ↑ Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". The Journal of Neuroscience. 18 (16): 6103–12. PMID 9698305.
  11. ↑ Quick MW (April 2002). "Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner". Proceedings of the National Academy of Sciences of the United States of America. 99 (8): 5686–91. doi:10.1073/pnas.082712899. PMC 122832Freely accessible. PMID 11960023.
  12. ↑ Deken SL, Beckman ML, Boos L, Quick MW (October 2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nature Neuroscience. 3 (10): 998–1003. doi:10.1038/79939. PMID 11017172.

Further reading

  • Nelson H, Mandiyan S, Nelson N (August 1990). "Cloning of the human brain GABA transporter". FEBS Letters. 269 (1): 181–4. doi:10.1016/0014-5793(90)81149-I. PMID 2387399. 
  • Bennett ER, Kanner BI (January 1997). "The membrane topology of GAT-1, a (Na+ + Cl-)-coupled gamma-aminobutyric acid transporter from rat brain". The Journal of Biological Chemistry. 272 (2): 1203–10. doi:10.1074/jbc.272.2.1203. PMID 8995422. 
  • Bismuth Y, Kavanaugh MP, Kanner BI (June 1997). "Tyrosine 140 of the gamma-aminobutyric acid transporter GAT-1 plays a critical role in neurotransmitter recognition". The Journal of Biological Chemistry. 272 (26): 16096–102. doi:10.1074/jbc.272.26.16096. PMID 9195904. 
  • DeFelipe J, González-Albo MC (February 1998). "Chandelier cell axons are immunoreactive for GAT-1 in the human neocortex". Neuroreport. 9 (3): 467–70. doi:10.1097/00001756-199802160-00020. PMID 9512391. 
  • Conti F, Melone M, De Biasi S, Minelli A, Brecha NC, Ducati A (June 1998). "Neuronal and glial localization of GAT-1, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in human cerebral cortex: with a note on its distribution in monkey cortex". The Journal of Comparative Neurology. 396 (1): 51–63. doi:10.1002/(SICI)1096-9861(19980622)396:1<51::AID-CNE5>3.0.CO;2-H. PMID 9623887. 
  • Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". The Journal of Neuroscience. 18 (16): 6103–12. PMID 9698305. 
  • Augood SJ, Waldvogel HJ, Münkle MC, Faull RL, Emson PC (January 1999). "Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus". Neuroscience. 88 (2): 521–34. doi:10.1016/S0306-4522(98)00226-7. PMID 10197772. 
  • Ong WY, Yeo TT, Balcar VJ, Garey LJ (October 1998). "A light and electron microscopic study of GAT-1-positive cells in the cerebral cortex of man and monkey". Journal of Neurocytology. 27 (10): 719–30. doi:10.1023/A:1006946717065. PMID 10640187. 
  • Deken SL, Beckman ML, Boos L, Quick MW (October 2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nature Neuroscience. 3 (10): 998–1003. doi:10.1038/79939. PMID 11017172. 
  • Whitworth TL, Quick MW (November 2001). "Substrate-induced regulation of gamma-aminobutyric acid transporter trafficking requires tyrosine phosphorylation". The Journal of Biological Chemistry. 276 (46): 42932–7. doi:10.1074/jbc.M107638200. PMID 11555659. 
  • Hachiya Y, Takashima S (November 2001). "Development of GABAergic neurons and their transporter in human temporal cortex". Pediatric Neurology. 25 (5): 390–6. doi:10.1016/S0887-8994(01)00348-4. PMID 11744314. 
  • Quick MW (April 2002). "Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner". Proceedings of the National Academy of Sciences of the United States of America. 99 (8): 5686–91. doi:10.1073/pnas.082712899. PMC 122832Freely accessible. PMID 11960023. 
  • Kanner BI (February 2003). "Transmembrane domain I of the gamma-aminobutyric acid transporter GAT-1 plays a crucial role in the transition between cation leak and transport modes". The Journal of Biological Chemistry. 278 (6): 3705–12. doi:10.1074/jbc.M210525200. PMID 12446715. 
  • Zomot E, Kanner BI (October 2003). "The interaction of the gamma-aminobutyric acid transporter GAT-1 with the neurotransmitter is selectively impaired by sulfhydryl modification of a conformationally sensitive cysteine residue engineered into extracellular loop IV". The Journal of Biological Chemistry. 278 (44): 42950–8. doi:10.1074/jbc.M209307200. PMID 12925537. 
  • Zhou Y, Bennett ER, Kanner BI (April 2004). "The aqueous accessibility in the external half of transmembrane domain I of the GABA transporter GAT-1 Is modulated by its ligands". The Journal of Biological Chemistry. 279 (14): 13800–8. doi:10.1074/jbc.M311579200. PMID 14744863. 
  • Hu JH, Ma YH, Jiang J, Yang N, Duan SH, Jiang ZH, Mei ZT, Fei J, Guo LH (January 2004). "Cognitive impairment in mice over-expressing gamma-aminobutyric acid transporter 1 (GAT1)". Neuroreport. 15 (1): 9–12. doi:10.1097/00001756-200401190-00003. PMID 15106822. 
  • Korkhov VM, Farhan H, Freissmuth M, Sitte HH (December 2004). "Oligomerization of the {gamma}-aminobutyric acid transporter-1 is driven by an interplay of polar and hydrophobic interactions in transmembrane helix II". The Journal of Biological Chemistry. 279 (53): 55728–36. doi:10.1074/jbc.M409449200. PMID 15496410. 

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