GABA transporter type 1: Difference between revisions

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== Clinical significance ==
== 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]].<ref>{{cite journal | vauthors = Volk D, Austin M, Pierri J, Sampson A, Lewis D | title = GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons | journal = The American Journal of Psychiatry | volume = 158 | issue = 2 | pages = 256–65 | date = February 2001 | pmid = 11156808 | doi = 10.1176/appi.ajp.158.2.256 }}</ref><ref name="Hashimoto">{{cite journal |last1=Hashimoto |first1=T |last2=Matsubara |first2=T |last3=Lewis |first3=DA |title=[Schizophrenia and cortical GABA neurotransmission]. |journal=Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica |date=2010 |volume=112 |issue=5 |pages=439-52 |pmid=20560363}}</ref>
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]].<ref>{{cite journal | vauthors = Volk D, Austin M, Pierri J, Sampson A, Lewis D | title = GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons | journal = The American Journal of Psychiatry | volume = 158 | issue = 2 | pages = 256–65 | date = February 2001 | pmid = 11156808 | doi = 10.1176/appi.ajp.158.2.256 }}</ref><ref name="Hashimoto">{{cite journal |last1=Hashimoto |first1=T |last2=Matsubara |first2=T |last3=Lewis |first3=DA |title=[Schizophrenia and cortical GABA neurotransmission]. |journal=Seishin Shinkeigaku Zasshi = Psychiatria et Neurologia Japonica |date=2010 |volume=112 |issue=5 |pages=439–52 |pmid=20560363}}</ref>


== Interactions ==
== Interactions ==


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| 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 }}</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 }}</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 }}</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>


== See also ==
== See also ==
Line 24: Line 24:
== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{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 }}
* {{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 = 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 = 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 }}
* {{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 }}
* {{cite journal | vauthors = DeFelipe J, González-Albo MC | title = Chandelier cell axons are immunoreactive for GAT-1 in the human neocortex | journal = NeuroReport | volume = 9 | issue = 3 | pages = 467–70 | date = February 1998 | pmid = 9512391 | doi = 10.1097/00001756-199802160-00020 }}
* {{cite journal | vauthors = DeFelipe J, González-Albo MC | title = Chandelier cell axons are immunoreactive for GAT-1 in the human neocortex | journal = NeuroReport | volume = 9 | issue = 3 | pages = 467–70 | date = February 1998 | pmid = 9512391 | doi = 10.1097/00001756-199802160-00020 | s2cid = 27446580 }}
* {{cite journal | vauthors = Conti F, Melone M, De Biasi S, Minelli A, Brecha NC, Ducati A | title = 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 | journal = The Journal of Comparative Neurology | volume = 396 | issue = 1 | pages = 51–63 | date = June 1998 | pmid = 9623887 | doi = 10.1002/(SICI)1096-9861(19980622)396:1<51::AID-CNE5>3.0.CO;2-H }}
* {{cite journal | vauthors = Conti F, Melone M, De Biasi S, Minelli A, Brecha NC, Ducati A | title = 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 | journal = The Journal of Comparative Neurology | volume = 396 | issue = 1 | pages = 51–63 | date = June 1998 | pmid = 9623887 | doi = 10.1002/(SICI)1096-9861(19980622)396:1<51::AID-CNE5>3.0.CO;2-H }}
* {{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| doi-access = free }}
* {{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 }}
* {{cite journal | vauthors = Augood SJ, Waldvogel HJ, Münkle MC, Faull RL, Emson PC | title = Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus | journal = Neuroscience | volume = 88 | issue = 2 | pages = 521–34 | date = January 1999 | pmid = 10197772 | doi = 10.1016/S0306-4522(98)00226-7 }}
* {{cite journal | vauthors = Augood SJ, Waldvogel HJ, Münkle MC, Faull RL, Emson PC | title = Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus | journal = Neuroscience | volume = 88 | issue = 2 | pages = 521–34 | date = January 1999 | pmid = 10197772 | doi = 10.1016/S0306-4522(98)00226-7 | s2cid = 2514970 }}
* {{cite journal | vauthors = Ong WY, Yeo TT, Balcar VJ, Garey LJ | title = A light and electron microscopic study of GAT-1-positive cells in the cerebral cortex of man and monkey | journal = Journal of Neurocytology | volume = 27 | issue = 10 | pages = 719–30 | date = October 1998 | pmid = 10640187 | doi = 10.1023/A:1006946717065 }}
* {{cite journal | vauthors = Ong WY, Yeo TT, Balcar VJ, Garey LJ | title = A light and electron microscopic study of GAT-1-positive cells in the cerebral cortex of man and monkey | journal = Journal of Neurocytology | volume = 27 | issue = 10 | pages = 719–30 | date = October 1998 | pmid = 10640187 | doi = 10.1023/A:1006946717065 | s2cid = 39552099 }}
* {{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 }}
* {{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 }}
* {{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 }}
Line 39: Line 39:
* {{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 }}
* {{cite journal | vauthors = Zhou Y, Bennett ER, Kanner BI | title = The aqueous accessibility in the external half of transmembrane domain I of the GABA transporter GAT-1 Is modulated by its ligands | journal = The Journal of Biological Chemistry | volume = 279 | issue = 14 | pages = 13800–8 | date = April 2004 | pmid = 14744863 | doi = 10.1074/jbc.M311579200 | doi-access = free }}
* {{cite journal | vauthors = Zhou Y, Bennett ER, Kanner BI | title = The aqueous accessibility in the external half of transmembrane domain I of the GABA transporter GAT-1 Is modulated by its ligands | journal = The Journal of Biological Chemistry | volume = 279 | issue = 14 | pages = 13800–8 | date = April 2004 | pmid = 14744863 | doi = 10.1074/jbc.M311579200 | doi-access = free }}
* {{cite journal | vauthors = Hu JH, Ma YH, Jiang J, Yang N, Duan SH, Jiang ZH, Mei ZT, Fei J, Guo LH | title = Cognitive impairment in mice over-expressing gamma-aminobutyric acid transporter 1 (GAT1) | journal = NeuroReport | volume = 15 | issue = 1 | pages = 9–12 | date = January 2004 | pmid = 15106822 | doi = 10.1097/00001756-200401190-00003 }}
* {{cite journal | vauthors = Hu JH, Ma YH, Jiang J, Yang N, Duan SH, Jiang ZH, Mei ZT, Fei J, Guo LH | title = Cognitive impairment in mice over-expressing gamma-aminobutyric acid transporter 1 (GAT1) | journal = NeuroReport | volume = 15 | issue = 1 | pages = 9–12 | date = January 2004 | pmid = 15106822 | doi = 10.1097/00001756-200401190-00003 | s2cid = 6407617 }}
* {{cite journal | vauthors = Korkhov VM, Farhan H, Freissmuth M, Sitte HH | title = Oligomerization of the {gamma}-aminobutyric acid transporter-1 is driven by an interplay of polar and hydrophobic interactions in transmembrane helix II | journal = The Journal of Biological Chemistry | volume = 279 | issue = 53 | pages = 55728–36 | date = December 2004 | pmid = 15496410 | doi = 10.1074/jbc.M409449200 | doi-access = free }}
* {{cite journal | vauthors = Korkhov VM, Farhan H, Freissmuth M, Sitte HH | title = Oligomerization of the {gamma}-aminobutyric acid transporter-1 is driven by an interplay of polar and hydrophobic interactions in transmembrane helix II | journal = The Journal of Biological Chemistry | volume = 279 | issue = 53 | pages = 55728–36 | date = December 2004 | pmid = 15496410 | doi = 10.1074/jbc.M409449200 | doi-access = free }}
{{refend}}
{{refend}}

Revision as of 08:58, 11 October 2020

SLC6A1
Identifiers
AliasesSLC6A1, GABATHG, GABATR, GAT1, MAE, GABA transporter 1, solute carrier family 6 member 1
External IDsOMIM: 137165; MGI: 95627; HomoloGene: 2290; GeneCards: SLC6A1; OMA:SLC6A1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003042
NM_001348250
NM_001348251
NM_001348252
NM_001348253

NM_178703

RefSeq (protein)

NP_003033
NP_001335179
NP_001335180
NP_001335181
NP_001335182

NP_848818

Location (UCSC)Chr 3: 10.99 – 11.04 MbChr 6: 114.26 – 114.29 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 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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000157103Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030310Ensembl, 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.
  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 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.
  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.
  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.
  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.
  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.

Further reading

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