Biology:GABA transporter 1
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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]
Clinical significance
Research 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][6]
Interactions
SLC6A1 has been shown to interact with STX1A.[7][8][9]
See also
References
- ↑ "Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24-p25". Genomics 29 (1): 302–4. September 1995. doi:10.1006/geno.1995.1253. PMID 8530094.
- ↑ "Entrez Gene: SLC6A1 solute carrier family 6 (neurotransmitter transporter, GABA), member 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6529.
- ↑ "Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity". Pharmacogenetics and Genomics 19 (1): 53–65. January 2009. doi:10.1097/FPC.0b013e328318b21a. PMID 19077666.
- ↑ "Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia". Frontiers in Systems Neuroscience 5: 63. 28 July 2011. doi:10.3389/fnsys.2011.00063. PMID 21847373.
- ↑ "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. February 2001. doi:10.1176/appi.ajp.158.2.256. PMID 11156808.
- ↑ Hashimoto, T; Matsubara, T; Lewis, DA (2010). "[Schizophrenia and cortical GABA neurotransmission].". Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 112 (5): 439-52. PMID 20560363.
- ↑ "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". The Journal of Neuroscience 18 (16): 6103–12. August 1998. doi:10.1523/JNEUROSCI.18-16-06103.1998. PMID 9698305.
- ↑ "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. April 2002. doi:10.1073/pnas.082712899. PMID 11960023.
- ↑ "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nature Neuroscience 3 (10): 998–1003. October 2000. doi:10.1038/79939. PMID 11017172.
Further reading
- "Cloning of the human brain GABA transporter". FEBS Letters 269 (1): 181–4. August 1990. doi:10.1016/0014-5793(90)81149-I. PMID 2387399.
- "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. January 1997. doi:10.1074/jbc.272.2.1203. PMID 8995422.
- "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. June 1997. doi:10.1074/jbc.272.26.16096. PMID 9195904.
- "Chandelier cell axons are immunoreactive for GAT-1 in the human neocortex". NeuroReport 9 (3): 467–70. February 1998. doi:10.1097/00001756-199802160-00020. PMID 9512391.
- "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. June 1998. doi:10.1002/(SICI)1096-9861(19980622)396:1<51::AID-CNE5>3.0.CO;2-H. PMID 9623887.
- "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". The Journal of Neuroscience 18 (16): 6103–12. August 1998. doi:10.1523/JNEUROSCI.18-16-06103.1998. PMID 9698305.
- "Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus". Neuroscience 88 (2): 521–34. January 1999. doi:10.1016/S0306-4522(98)00226-7. PMID 10197772.
- "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. October 1998. doi:10.1023/A:1006946717065. PMID 10640187.
- "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nature Neuroscience 3 (10): 998–1003. October 2000. doi:10.1038/79939. PMID 11017172.
- "Substrate-induced regulation of gamma-aminobutyric acid transporter trafficking requires tyrosine phosphorylation". The Journal of Biological Chemistry 276 (46): 42932–7. November 2001. doi:10.1074/jbc.M107638200. PMID 11555659.
- "Development of GABAergic neurons and their transporter in human temporal cortex". Pediatric Neurology 25 (5): 390–6. November 2001. doi:10.1016/S0887-8994(01)00348-4. PMID 11744314.
- "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. April 2002. doi:10.1073/pnas.082712899. PMID 11960023.
- "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. February 2003. doi:10.1074/jbc.M210525200. PMID 12446715.
- "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. October 2003. doi:10.1074/jbc.M209307200. PMID 12925537.
- "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. April 2004. doi:10.1074/jbc.M311579200. PMID 14744863.
- "Cognitive impairment in mice over-expressing gamma-aminobutyric acid transporter 1 (GAT1)". NeuroReport 15 (1): 9–12. January 2004. doi:10.1097/00001756-200401190-00003. PMID 15106822.
- "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. December 2004. 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.
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