The Na⁺/Cl^- transporter family SLC6, includes DAT, a monoamine transporter, important for regulating extracellular levels of dopamine. It does so by taking up dopamine from the synaptic cleft via the co-transport of Na⁺ and Cl^- down their electrochemical gradients¹. The removal of dopamine by DAT remains the most important means to control the extracellular lifetime of the neurotransmitter and notably, the ending of dopaminergic neurotransmission². Transporters for serotonin, norepinephrine, GABA and glycine also belong to this family³.

These receptors have 12 transmembrane spanning domains and intracellular N- and C-termini. DAT is also subject to post translational modifications such as phosphorylation, important for its regulation¹. It also possesses a large extracellular domain which undergoes N-glycosylation, important for the proper targeting of the transporter to the plasma membrane¹. DAT is expressed in dopaminergic cell bodies and terminals and can therefore serve as a marker for these neurons⁴. DAT is also expressed in the retina, gastrointestinal tract, lung, kidney, pancreas and lymphocytes².

DAT plays an important role in movement as well as reward, learning and memory⁵. Its malfunction, which leads to dopaminergic dysregulation, has been associated with ADHD, schizophrenia, as well as Parkinson’s disease². DAT is the main target for cocaine, amphetamine and methamphetamine psychostimulants, which mainly increase locomotor activities².