GABA transporter type 1: Difference between revisions

SLC6A1
Identifiers
Aliases	SLC6A1, GABATHG, GABATR, GAT1, MAE, GABA transporter 1, solute carrier family 6 member 1
External IDs	OMIM: 137165; MGI: 95627; HomoloGene: 2290; GeneCards: SLC6A1; OMA:SLC6A1 - orthologs
Gene location (Human)
Chr.	Chromosome 3 (human)
End	11,039,247 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	114,294,493 bp
RNA expression pattern
	Top expressed in
	external globus pallidus; ; cerebellar vermis; ; subthalamic nucleus; ; postcentral gyrus; ; superior vestibular nucleus; ; prefrontal cortex; ; orbitofrontal cortex; ; caudate nucleus; ; amygdala; ; superior frontal gyrus;
	Top expressed in
	dorsal tegmental nucleus; ; cerebellar vermis; ; globus pallidus; ; ventral tegmental area; ; lateral hypothalamus; ; superior colliculus; ; dorsomedial hypothalamic nucleus; ; paraventricular nucleus of hypothalamus; ; medial vestibular nucleus; ; mammillary body;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	metal ion binding; neurotransmitter:sodium symporter activity; symporter activity; gamma-aminobutyric acid:sodium symporter activity; neurotransmitter binding; protein binding;
Cellular component	integral component of membrane; membrane; plasma membrane; integral component of plasma membrane; neuron projection; cell surface; axon; GABA-ergic synapse; integral component of postsynaptic membrane; integral component of presynaptic membrane;
Biological process	chemical synaptic transmission; gamma-aminobutyric acid transport; transmembrane transport; neurotransmitter transport; learning; response to toxic substance; response to sucrose; response to organic substance; response to organonitrogen compound; response to lead ion; positive regulation of gamma-aminobutyric acid secretion; response to organic cyclic compound; response to purine-containing compound; negative regulation of synaptic transmission, GABAergic; response to estradiol; response to cocaine; protein homooligomerization; response to calcium ion; gamma-aminobutyric acid import;
	Sources:Amigo / QuickGO
Orthologs
	6529
	232333
	ENSG00000157103
	ENSMUSG00000030310
	P30531
	P31648
	NM_003042; NM_001348250; NM_001348251; NM_001348252; NM_001348253
	NM_178703
	NP_003033; NP_001335179; NP_001335180; NP_001335181; NP_001335182
	NP_848818
	Wikidata
View/Edit Human	View/Edit Mouse

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Revision as of 02:23, 2 January 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]

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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ 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. 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.

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. 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.

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

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000157103 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030310 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8530094-5] 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.

[entrez-6] "Entrez Gene: SLC6A1 solute carrier family 6 (neurotransmitter transporter, GABA), member 1".

[pmid19077666-7] 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 2791799. 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. PMC 3148782. PMID 21847373.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[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.

[Hashimoto-10] 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.

[pmid9698305-11] 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.

[pmid11960023-12] 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.

[pmid11017172-13] 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.

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 == Further reading ==
 {{refbegin | 2}}
-* {{cite journal | vauthors = Nelson H, Mandiyan S, Nelson N | title = Cloning of the human brain GABA transporter | journal = FEBS Letters | volume = 269 | issue = 1 | pages = 181–4 | date = August 1990 | pmid = 2387399 | doi = 10.1016/0014-5793(90)81149-I | s2cid = 34636220 }}
+* {{cite journal | vauthors = Nelson H, Mandiyan S, Nelson N | title = Cloning of the human brain GABA transporter | journal = FEBS Letters | volume = 269 | issue = 1 | pages = 181–4 | date = August 1990 | pmid = 2387399 | doi = 10.1016/0014-5793(90)81149-I | s2cid = 34636220 | doi-access = free }}
 * {{cite journal | vauthors = Bennett ER, Kanner BI | title = The membrane topology of GAT-1, a (Na+ + Cl-)-coupled gamma-aminobutyric acid transporter from rat brain | journal = The Journal of Biological Chemistry | volume = 272 | issue = 2 | pages = 1203–10 | date = January 1997 | pmid = 8995422 | doi = 10.1074/jbc.272.2.1203 | doi-access = free }}
 * {{cite journal | vauthors = Bismuth Y, Kavanaugh MP, Kanner BI | title = Tyrosine 140 of the gamma-aminobutyric acid transporter GAT-1 plays a critical role in neurotransmitter recognition | journal = The Journal of Biological Chemistry | volume = 272 | issue = 26 | pages = 16096–102 | date = June 1997 | pmid = 9195904 | doi = 10.1074/jbc.272.26.16096 | doi-access = free }}

v t e Membrane transport protein: neurotransmitter transporters (TC 2.A.1.2)
Vesicular	Vesicular monoamine VMAT1 VMAT2 Vesicular acetylcholine Vesicular glutamate Vesicular GABA
Other	Monoamine DAT NET SERT PMAT Excitatory amino-acid transporter GABA transporter

Revision as of 02:23, 2 January 2021

Function

Clinical significance

Interactions

See also

References

Further reading