TY - JOUR T1 - SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation JF - Pharmacological Reviews JO - Pharmacol Rev SP - 585 LP - 640 DO - 10.1124/pr.108.000869 VL - 63 IS - 3 AU - Anders S. Kristensen AU - Jacob Andersen AU - Trine N. Jørgensen AU - Lena Sørensen AU - Jacob Eriksen AU - Claus J. Loland AU - Kristian Strømgaard AU - Ulrik Gether A2 - Simonsen, Ulf Y1 - 2011/09/01 UR - http://pharmrev.aspetjournals.org/content/63/3/585.abstract N2 - The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na+/Cl−-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy. Furthermore, psychostimulants such as cocaine and amphetamines have the SLC6 NTTs as primary targets. Beginning with the determination of a high-resolution structure of a prokaryotic homolog of the mammalian SLC6 transporters in 2005, the understanding of the molecular structure, function, and pharmacology of these proteins has advanced rapidly. Furthermore, intensive efforts have been directed toward understanding the molecular and cellular mechanisms involved in regulation of the activity of this important class of transporters, leading to new methodological developments and important insights. This review provides an update of these advances and their implications for the current understanding of the SLC6 NTTs. ER -