GABA transporter 1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
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RefSeq (mRNA)

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RefSeq (protein)

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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.[1][2]

Function

GAT1 is a gamma-aminobutyric acid (GABA) transporter, which removes GABA from the synaptic cleft.[3] GABA Transporter 1 uses energy from the dissipation of a Na+ gradient, aided by the presence of a Cl gradient, to translocate GABA across CNS neuronal membranes. The stoichiometry for GABA Transporter 1 is 2 Na+: 1 Cl: 1 GABA.[4]

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.[5]

Interactions

SLC6A1 has been shown to interact with STX1A.[6][7][8]

See also

References

  1. 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.
  2. "Entrez Gene: SLC6A1 solute carrier family 6 (neurotransmitter transporter, GABA), member 1".
  3. 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 2791799. PMID 19077666.
  4. 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. PMC 3148782. PMID 21847373.
  5. 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.
  6. 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.
  7. 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 122832. PMID 11960023.
  8. 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 122832. 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.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.