Serotonin transporter (SLC6A4) (SERT)

The serotonin transporter (SERT), encoded by the SLC6A4 gene, is an integral membrane protein responsible for the high-affinity reuptake of serotonin (5-HT) from the synaptic cleft back into the presynaptic neuron (UniProt P31645). This transport process is driven by the electrochemical gradient of sodium and chloride ions and is the primary mechanism for terminating serotonergic signaling in the central nervous system (NIH/NCBI Gene). The central S1 substrate site is the primary binding pocket located in the core of the transporter's transmembrane bundle, where both the endogenous substrate and most clinical antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), bind (Coleman et al., Nature 2016). By occupying the S1 site, drugs prevent the transport of serotonin, leading to increased neurotransmitter availability and enhanced post-synaptic signaling, which is a cornerstone in the treatment of depression and anxiety (StatPearls). Beyond the brain, SERT is also expressed in blood platelets and the gastrointestinal tract, where it regulates peripheral serotonin levels and contributes to the drug's side effect profile, such as gastrointestinal upset and bleeding risks (PubMed).

Other names

5-HTT5-hydroxytryptamine transporterSodium-dependent serotonin transporterSolute carrier family 6 member 4HTTOCD1

Competitive inhibition of serotonin reuptake by binding to the central S1 substrate site, thereby increasing the concentration and duration of serotonin in the synaptic cleft.