SERTtransporterin

SERTtransporterin, more commonly referred to as the serotonin transporter (SERT or 5-HTT), is a membrane protein encoded by the SLC6A4 gene. It is a member of the solute carrier (SLC) family and functions primarily to reuptake serotonin (5-hydroxytryptamine) from the synaptic cleft back into presynaptic neurons. This reuptake mechanism terminates serotonin signaling and regulates the availability of the neurotransmitter for subsequent synaptic transmission. The transporter is a 12‑transmembrane domain protein that operates via a sodium and chloride co‑transport mechanism, tightly coupling the movement of serotonin to ion gradients.

SERTtransporterin is highly expressed in the central nervous system, particularly in raphe nuclei and throughout serotonergic projections. It is also found in peripheral tissues such as platelets, enterochromaffin cells, and the gallbladder. Genetic polymorphisms in the SLC6A4 promoter, such as the 5-HTTLPR short and long alleles, influence transcriptional activity and have been associated with altered susceptibility to psychiatric disorders, personality traits, and response to selective serotonin reuptake inhibitors (SSRIs). The transporter’s structure has been elucidated through cryo‑electron microscopy, revealing ligand binding sites and conformational changes during the transport cycle.

Pharmacologically, SERTtransporterin is the primary target of SSRIs (e.g., fluoxetine, sertraline) and certain antidepressants, as well as the antipsychotic clozapine and the designer drug MDMA. Inhibition of the transporter increases extracellular serotonin, alleviating symptoms of depression and anxiety. Precise modulation of SERT activity remains a focus in neuropsychiatric research, with implications for developing novel therapeutics and understanding the molecular basis of serotonin‑related disorders.