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== Function == |
== Function == |
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GAT1 is a [[gamma-aminobutyric acid]] (GABA) transporter, which removes [[GABA]] from the synaptic cleft.<ref name="pmid19077666">{{cite journal | vauthors = 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 | title = Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity | journal = Pharmacogenetics and Genomics | volume = 19 | issue = 1 | pages = 53–65 | date = January 2009 | pmid = 19077666 | pmc = 2791799 | doi = 10.1097/FPC.0b013e328318b21a }}</ref> GABA Transporter 1 uses energy from the dissipation of a Na<sup>+</sup> gradient, aided by the presence of a Cl<sup>−</sup> gradient, to translocate GABA across CNS neuronal membranes. The stoichiometry for GABA Transporter 1 is 2 Na<sup>+</sup>: 1 Cl<sup>−</sup>: 1 GABA.<ref>{{cite journal | vauthors = Jin XT, Galvan A, Wichmann T, Smith Y | title = Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia | journal = Frontiers in Systems Neuroscience | volume = 5 | pages = 63 | date = 28 July 2011 | pmid = 21847373 | doi = 10.3389/fnsys.2011.00063 | pmc=3148782}}</ref> |
GAT1 is a [[gamma-aminobutyric acid]] (GABA) transporter, which removes [[GABA]] from the synaptic cleft.<ref name="pmid19077666">{{cite journal | vauthors = 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 | title = Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity | journal = Pharmacogenetics and Genomics | volume = 19 | issue = 1 | pages = 53–65 | date = January 2009 | pmid = 19077666 | pmc = 2791799 | doi = 10.1097/FPC.0b013e328318b21a }}</ref> GABA Transporter 1 uses energy from the dissipation of a Na<sup>+</sup> gradient, aided by the presence of a Cl<sup>−</sup> gradient, to translocate GABA across CNS neuronal membranes. The stoichiometry for GABA Transporter 1 is 2 Na<sup>+</sup>: 1 Cl<sup>−</sup>: 1 GABA.<ref>{{cite journal | vauthors = Jin XT, Galvan A, Wichmann T, Smith Y | title = Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia | journal = Frontiers in Systems Neuroscience | volume = 5 | pages = 63 | date = 28 July 2011 | pmid = 21847373 | doi = 10.3389/fnsys.2011.00063 | pmc=3148782| doi-access = free }}</ref> |
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== Clinical significance == |
== Clinical significance == |
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== Interactions == |
== Interactions == |
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SLC6A1 has been shown to [[Protein-protein interaction|interact]] with [[STX1A]].<ref name = pmid9698305>{{cite journal | vauthors = Beckman ML, Bernstein EM, Quick MW | title = Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A | journal = The Journal of Neuroscience | volume = 18 | issue = 16 | pages = 6103–12 | date = August 1998 | pmid = 9698305 | doi = 10.1523/JNEUROSCI.18-16-06103.1998| pmc = 6793212 | doi-access = free }}</ref><ref name = pmid11960023>{{cite journal | vauthors = Quick MW | title = Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 8 | pages = 5686–91 | date = April 2002 | pmid = 11960023 | pmc = 122832 | doi = 10.1073/pnas.082712899 | bibcode = 2002PNAS...99.5686Q }}</ref><ref name = pmid11017172>{{cite journal | vauthors = Deken SL, Beckman ML, Boos L, Quick MW | title = Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A | journal = Nature Neuroscience | volume = 3 | issue = 10 | pages = 998–1003 | date = October 2000 | pmid = 11017172 | doi = 10.1038/79939 | s2cid = 11312913 }}</ref> |
SLC6A1 has been shown to [[Protein-protein interaction|interact]] with [[STX1A]].<ref name = pmid9698305>{{cite journal | vauthors = Beckman ML, Bernstein EM, Quick MW | title = Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A | journal = The Journal of Neuroscience | volume = 18 | issue = 16 | pages = 6103–12 | date = August 1998 | pmid = 9698305 | doi = 10.1523/JNEUROSCI.18-16-06103.1998| pmc = 6793212 | doi-access = free }}</ref><ref name = pmid11960023>{{cite journal | vauthors = Quick MW | title = Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 8 | pages = 5686–91 | date = April 2002 | pmid = 11960023 | pmc = 122832 | doi = 10.1073/pnas.082712899 | bibcode = 2002PNAS...99.5686Q | doi-access = free }}</ref><ref name = pmid11017172>{{cite journal | vauthors = Deken SL, Beckman ML, Boos L, Quick MW | title = Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A | journal = Nature Neuroscience | volume = 3 | issue = 10 | pages = 998–1003 | date = October 2000 | pmid = 11017172 | doi = 10.1038/79939 | s2cid = 11312913 }}</ref> |
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== See also == |
== See also == |
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* {{cite journal | vauthors = Whitworth TL, Quick MW | title = Substrate-induced regulation of gamma-aminobutyric acid transporter trafficking requires tyrosine phosphorylation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 42932–7 | date = November 2001 | pmid = 11555659 | doi = 10.1074/jbc.M107638200 | doi-access = free }} |
* {{cite journal | vauthors = Whitworth TL, Quick MW | title = Substrate-induced regulation of gamma-aminobutyric acid transporter trafficking requires tyrosine phosphorylation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 42932–7 | date = November 2001 | pmid = 11555659 | doi = 10.1074/jbc.M107638200 | doi-access = free }} |
||
* {{cite journal | vauthors = Hachiya Y, Takashima S | title = Development of GABAergic neurons and their transporter in human temporal cortex | journal = Pediatric Neurology | volume = 25 | issue = 5 | pages = 390–6 | date = November 2001 | pmid = 11744314 | doi = 10.1016/S0887-8994(01)00348-4 }} |
* {{cite journal | vauthors = Hachiya Y, Takashima S | title = Development of GABAergic neurons and their transporter in human temporal cortex | journal = Pediatric Neurology | volume = 25 | issue = 5 | pages = 390–6 | date = November 2001 | pmid = 11744314 | doi = 10.1016/S0887-8994(01)00348-4 }} |
||
* {{cite journal | vauthors = Quick MW | title = Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 8 | pages = 5686–91 | date = April 2002 | pmid = 11960023 | pmc = 122832 | doi = 10.1073/pnas.082712899 | bibcode = 2002PNAS...99.5686Q }} |
* {{cite journal | vauthors = Quick MW | title = Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 8 | pages = 5686–91 | date = April 2002 | pmid = 11960023 | pmc = 122832 | doi = 10.1073/pnas.082712899 | bibcode = 2002PNAS...99.5686Q | doi-access = free }} |
||
* {{cite journal | vauthors = Kanner BI | title = Transmembrane domain I of the gamma-aminobutyric acid transporter GAT-1 plays a crucial role in the transition between cation leak and transport modes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 6 | pages = 3705–12 | date = February 2003 | pmid = 12446715 | doi = 10.1074/jbc.M210525200 | doi-access = free }} |
* {{cite journal | vauthors = Kanner BI | title = Transmembrane domain I of the gamma-aminobutyric acid transporter GAT-1 plays a crucial role in the transition between cation leak and transport modes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 6 | pages = 3705–12 | date = February 2003 | pmid = 12446715 | doi = 10.1074/jbc.M210525200 | doi-access = free }} |
||
* {{cite journal | vauthors = Zomot E, Kanner BI | title = 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 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 44 | pages = 42950–8 | date = October 2003 | pmid = 12925537 | doi = 10.1074/jbc.M209307200 | doi-access = free }} |
* {{cite journal | vauthors = Zomot E, Kanner BI | title = 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 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 44 | pages = 42950–8 | date = October 2003 | pmid = 12925537 | doi = 10.1074/jbc.M209307200 | doi-access = free }} |
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Revision as of 04:31, 30 August 2021
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 is a gamma-aminobutyric acid (GABA) transporter, which removes GABA from the synaptic cleft.[7] 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.[8]
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.[9][10]
Interactions
SLC6A1 has been shown to interact with STX1A.[11][12][13]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000157103 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030310 – 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.
- ^ 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.
- ^ "Entrez Gene: SLC6A1 solute carrier family 6 (neurotransmitter transporter, GABA), member 1".
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. doi:10.1523/JNEUROSCI.18-16-06103.1998. PMC 6793212. PMID 9698305.
- ^ 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. Bibcode:2002PNAS...99.5686Q. doi:10.1073/pnas.082712899. PMC 122832. PMID 11960023.
- ^ 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. S2CID 11312913.
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. S2CID 34636220.
- 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. S2CID 27446580.
- 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. doi:10.1523/JNEUROSCI.18-16-06103.1998. PMC 6793212. 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. S2CID 2514970.
- 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. S2CID 39552099.
- 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. S2CID 11312913.
- 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. Bibcode:2002PNAS...99.5686Q. 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. S2CID 6407617.
- 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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