Serotonin transporter (SERT), Norepinephrine transporter (NET), Dopamine transporter (DAT) (SERT, NET, DAT)

The serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) are sodium- and chloride-dependent membrane proteins belonging to the solute carrier family 6 (SLC6). These monoamine transporters are responsible for the termination of neurotransmission—removing serotonin, norepinephrine, or dopamine from the synaptic cleft back into presynaptic neurons. Their structure features twelve transmembrane helices and a conserved central substrate binding site. The pharmacological and genetic importance of these transporters underlies the mechanism-of-action for major classes of antidepressants, psychostimulants, and drugs of abuse, which block reuptake and elevate synaptic concentrations of their respective neurotransmitters. Mutations, misfolding, or altered expression of these transporters have been implicated in many neuropsychiatric and neurodegenerative disorders, making them principal subjects of drug discovery and clinical investigation.

Other names

5-HT transporterSLC6A4Noradrenaline transporterSLC6A2Dopamine transporterSLC6A3DAT1

Inhibition of reuptake, thereby increasing synaptic monoamine levels; Competitive binding at central substrate site; Allosteric modulation (in some cases, e.g., SERT)