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Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6

  • The ABC of Solute carriers
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Abstract

The SLC6 family is a diverse set of transporters that mediate solute translocation across cell plasma membranes by coupling solute transport to the cotransport of sodium and chloride down their electrochemical gradients. These transporters probably have 12 transmembrane domains, with cytoplasmic N- and C-terminal tails, and at least some may function as homo-oligomers. Family members include the transporters for the inhibitory neurotransmitters GABA and glycine, the aminergic transmitters norepinephrine, serotonin, and dopamine, the osmolytes betaine and taurine, the amino acid proline, and the metabolic compound creatine. In addition, this family includes a system B0+ cationic and neutral amino acid transporter, and two transporters for which the solutes are unknown. In general, SLC6 transporters act to regulate the level of extracellular solute concentrations. In the central and the peripheral nervous system, these transporters can regulate signaling among neurons, are the sites of action of various drugs of abuse, and naturally occurring mutations in several of these proteins are associated with a variety of neurological disorders. For example, transgenic animals lacking specific aminergic transporters show profoundly disturbed behavioral phenotypes and probably represent excellent systems for investigating psychiatric disease. SLC6 transporters are also found in many non-neural tissues, including kidney, intestine, and testis, consistent with their diverse physiological roles. Transporters in this family represent attractive therapeutic targets because they are subject to multiple forms of regulation by many different signaling cascades, and because a number of pharmacological agents have been identified that act specifically on these proteins.

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Acknowledgements

This work was supported in part by National Institutes of Health Grants DA11978, DA13261 to MEAR, and DA10509, MH61468 to MWQ.

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  1. Department of Biological Sciences, University of Southern California, HNB 228, 3641 Watt Way, Los Angeles, CA 90089-2520, USA

    Michael W. Quick

  2. Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, Illinois, USA

    Nian-Hang Chen & Maarten E. A. Reith

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Chen, NH., Reith, M.E.A. & Quick, M.W. Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6. Pflugers Arch - Eur J Physiol 447, 519–531 (2004). https://doi.org/10.1007/s00424-003-1064-5

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