Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

GABA Transporters

Reference work entry
First Online:
DOI: https://doi.org/10.1007/978-3-319-67199-4_329
How to cite

Synonyms

 Betaine/GABA transporter-1 (BGT-1);  GAT-1;  GAT-2;  GAT-3

Introduction

There are two nomenclatures for GABA transporters (GATs). In the rat/human nomenclature, GABA transporters are called GAT-1, betaine/GABA transporter-1 (BGT-1), GAT-2, and GAT-3 (Borden et al. 1992). In the mouse nomenclature, GATs are called GAT1, GAT2, GAT3, and GAT4 (without hyphen, Liu et al. 1993). They were encoded by the genes SLC6A1 (for GAT-1) and SLC6A11–13 (for GAT-3, BGT-1, and GAT-2, respectively). In this review, the rat/human nomenclature will be used.

Historical Background

The amino acid γ-amino butyric acid (GABA) is the main inhibitory neurotransmitter in the adult brain. The actions of GABA are mediated via two distinct classes of receptors: ionotropic ( GABAA and GABAc) and metabotropic (GABAB) receptors (Farrant and Kaila 2007). For adequate synaptic transmission, the released GABA has to be rapidly sequestered from the synaptic cleft by high affinity GABA transporters. Experiments...

This is a preview of subscription content, log in to check access.

References

  1. Allen NJ, Karadottir R, Attwell D. Reversal or reduction of glutamate and GABA transport in CNS pathology and therapy. Pflugers Arch. 2004;449:132–42.  https://doi.org/10.1007/s00424-004-1318-x.CrossRefPubMedGoogle Scholar
  2. Attwell D, Barbour B, Szatkowski M. Nonvesicular release of neurotransmitter. Neuron. 1993;11:401–7.PubMedGoogle Scholar
  3. Beckman ML, Bernstein EM, Quick MW. Multiple G protein-coupled receptors initiate protein kinase C redistribution of GABA transporters in hippocampal neurons. J Neurosci. 1999;19:RC9.PubMedGoogle Scholar
  4. Beckman ML, Quick MW. Neurotransmitter transporters: regulators of function and functional regulation. J Membr Biol. 1998;164:1–10.PubMedGoogle Scholar
  5. Bernstein EM, Quick MW. Regulation of gamma-aminobutyric acid (GABA) transporters by extracellular GABA. J Biol Chem. 1999;274:889–95.PubMedGoogle Scholar
  6. Borden LA. GABA transporter heterogeneity: pharmacology and cellular localization. Neurochem Int. 1996;29:335–56.PubMedGoogle Scholar
  7. Borden LA, Smith KE, Hartig PR, Branchek TA, Weinshank RL. Molecular heterogeneity of the gamma-aminobutyric acid (GABA) transport system. Cloning of two novel high affinity GABA transporters from rat brain. J Biol Chem. 1992;267:21098–104.PubMedGoogle Scholar
  8. Conti F, Minelli A, Melone M. GABA transporters in the mammalian cerebral cortex: localization, development and pathological implications. Brain Res Brain Res Rev. 2004;45:196–212.  https://doi.org/10.1016/j.brainresrev.2004.03.003.CrossRefPubMedGoogle Scholar
  9. Deken SL, Wang D, Quick MW. Plasma membrane GABA transporters reside on distinct vesicles and undergo rapid regulated recycling. J Neurosci. 2003;23:1563–8.PubMedGoogle Scholar
  10. Farrant M, Kaila K. The cellular, molecular and ionic basis of GABA(A) receptor signalling. Prog Brain Res. 2007;160:59–87.  https://doi.org/10.1016/S0079-6123(06)60005-8.CrossRefPubMedGoogle Scholar
  11. Kempson SA, Zhou Y, Danbolt NC. The betaine/GABA transporter and betaine: roles in brain, kidney, and liver. Front Physiol. 2014;5:159.  https://doi.org/10.3389/fphys.2014.00159.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Liu QR, Lopez-Corcuera B, Mandiyan S, Nelson H, Nelson N. Molecular characterization of four pharmacologically distinct gamma-aminobutyric acid transporters in mouse brain. J Biol Chem. 1993;268:2106–12.PubMedGoogle Scholar
  13. Masson J, Sagne C, Hamon M, El Mestikawy S. Neurotransmitter transporters in the central nervous system. Pharmacol Rev. 1999;51:439–64.PubMedGoogle Scholar
  14. Nelson N. The family of Na+/Cl− neurotransmitter transporters. J Neurochem. 1998;71:1785–803.PubMedGoogle Scholar
  15. Richerson GB, Wu Y. Dynamic equilibrium of neurotransmitter transporters: not just for reuptake anymore. J Neurophysiol. 2003;90:1363–74.  https://doi.org/10.1152/jn.00317.2003.CrossRefPubMedGoogle Scholar
  16. Richerson GB, Wu YM. Role of the GABA transporter in epilepsy. Adv Exp Med Biol. 2004;548:76–91.PubMedGoogle Scholar
  17. Schleimer SB, Hinton T, Dixon G, Johnston GA. GABA transporters GAT-1 and GAT-3 in the human dorsolateral prefrontal cortex in schizophrenia. Neuropsychobiology. 2004;50:226–30.  https://doi.org/10.1159/000079975.CrossRefPubMedGoogle Scholar
  18. Son WY, Lee HJ, Yoon HK, Kang SG, Park YM, Yang HJ, Choi JE, An H, Seo HK, Kim L. GABA transporter SLC6A11 gene polymorphism associated with tardive dyskinesia. Nord J Psychiatry. 2014;68:123–8.  https://doi.org/10.3109/08039488.2013.780260.CrossRefPubMedGoogle Scholar
  19. Thoeringer CK, Ripke S, Unschuld PG, Lucae S, Ising M, Bettecken T, Uhr M, Keck ME, Mueller-Myhsok B, Holsboer F, Binder EB, Erhardt A. The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders. J Neural Transm. 2009;116:649–57.  https://doi.org/10.1007/s00702-008-0075-y.CrossRefPubMedGoogle Scholar
  20. Wu Y, Wang W, Diez-Sampedro A, Richerson GB. Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1. Neuron. 2007;56:851–65.  https://doi.org/10.1016/j.neuron.2007.10.021.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E. Crystal structure of a bacterial homologue of Na+/Cl−-dependent neurotransmitter transporters. Nature. 2005;437:215–23.  https://doi.org/10.1038/nature03978.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute of PhysiologyUniversity Medical Center MainzMainzGermany