Serotonin transporter (SERT) and Norepinephrine transporter (NET) (SERT (for serotonin transporter), NET (for norepinephrine transporter))

The serotonin transporter (SERT) and norepinephrine transporter (NET) are integral membrane proteins, primarily localized to presynaptic neuronal terminals[1][4][6]. They use the sodium and chloride gradient across the membrane to drive reuptake of released serotonin and norepinephrine, respectively, thus terminating neurotransmitter signaling and regulating extracellular concentrations. Both transporters have a central substrate binding site surrounded by multiple transmembrane helices, and at least one allosteric site that modulates ligand binding and release[1][2][5]. Inhibitors, including widely used antidepressant drugs, bind to these sites and block the reuptake process, increasing synaptic neurotransmitter availability and modulating mood, cognition, and pain. Both proteins play a critical role in the pathophysiology and therapy of neuropsychiatric disease, making them important targets for pharmacological intervention[1][2][3][4][5][6].

Other names

5-HT transporterSLC6A4 (for SERT)Noradrenaline transporterSLC6A2 (for NET)Monoamine transporter family

Inhibition of reuptake (blockade of central substrate-binding site by antidepressants or inhibitors)[1][2][3][5]; Allosteric modulation (some SSRIs occupy both central and allosteric binding sites, slowing dissociation and prolonged effect)[1][5]; Reversal of transport direction (certain amphetamines cause neurotransmitter efflux)[3]