sert

SERT, or the serotonin transporter, is a membrane protein that reuptakes serotonin (5-HT) from the synaptic cleft. In humans it is encoded by the SLC6A4 gene and belongs to the solute carrier 6 (SLC6) family of neurotransmitter transporters. SERT has 12 transmembrane domains and operates as a sodium- and chloride-dependent transporter that uses ion gradients to move serotonin into presynaptic neurons, thereby terminating the signal and enabling recycling of the neurotransmitter. It is highly expressed on serotonergic neurons in the brain, particularly projections from the raphe nuclei, and is also present in platelets and various peripheral tissues, including the gastrointestinal tract.

The regulation and distribution of SERT influence serotonin clearance and signaling. The promoter region of SLC6A4 contains the 5-HTTLPR polymorphism with short and long alleles that influence transcriptional activity and transporter expression. Additional genetic variants and epigenetic factors can modulate SERT levels, contributing to individual differences in serotonin clearance and susceptibility to stress-related disorders. SERT function can be affected by environmental factors, age, and disease states, with alterations in transporter availability observed in some psychiatric conditions.

Clinically, SERT is the primary target of selective serotonin reuptake inhibitors (SSRIs), a major class of antidepressants and anxiolytics. By inhibiting SERT, SSRIs increase extracellular serotonin and enhance serotonergic signaling, which is associated with improvements in mood and anxiety symptoms for many patients. SERT dysfunction or altered availability has been implicated in mood and anxiety disorders, obsessive-compulsive disorder, and other conditions in various studies. Imaging methods using radioligands measure SERT density to study serotonergic function in vivo, supporting research into psychiatric disorders and treatment effects. See also SLC6A4.