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Sodium-dependent serotonin transporter (SERT) (SERT)

Target
SERT
Molecular classification
Transporter, Solute carrier family 6 member 4, Sodium-dependent neurotransmitter transporter
01

Overview

The Sodium-dependent serotonin transporter (SERT), encoded by the SLC6A4 gene, is an integral membrane protein responsible for the reuptake of serotonin (5-hydroxytryptamine) from the synaptic cleft back into the presynaptic neuron (UniProt P31645). This process is the primary mechanism for terminating serotonergic signaling in the central nervous system and regulating the concentration of serotonin available for receptor binding (NCBI Gene ID: 6532). Beyond the brain, SERT is also expressed in platelets and the gastrointestinal tract, where it modulates peripheral serotonin levels (PubMed: 15173104). Dysregulation of SERT is strongly linked to various psychiatric and neurological conditions, including major depressive disorder, anxiety, and obsessive-compulsive disorder (StatPearls: SSRIs). Consequently, SERT is one of the most significant therapeutic targets in psychiatry, serving as the primary site of action for Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) (PubChem: SLC6A4). These drugs bind to the transporter and inhibit its function, thereby increasing extracellular serotonin levels and enhancing neurotransmission (PubMed: 10446076).

Other names
5-HTTSerotonin transporterSolute carrier family 6 member 45-hydroxytryptamine transporterSerotonin reuptake pump5-HT reuptake transporter
02

Mechanism of action

Inhibition of the sodium-dependent reuptake of serotonin (5-HT) from the synaptic cleft into the presynaptic neuron, thereby increasing the duration and intensity of serotonergic signaling (StatPearls: SSRIs).

03

Biological functions

Serotonin reuptakeRegulation of synaptic serotonin concentrationPlatelet serotonin uptakeModulation of enteric nervous system signaling
04

Disease associations

Major depressive disorderGeneralized anxiety disorderObsessive-compulsive disorderPanic disorderPost-traumatic stress disorderIrritable bowel syndrome
05

Safety considerations

Serotonin syndrome (PubMed: 29083131)Increased risk of suicidal ideation in children and young adults (StatPearls: SSRIs)Sexual dysfunction (PubMed: 29083131)Gastrointestinal distress (PubMed: 29083131)Antidepressant discontinuation syndrome (PubMed: 29083131)
06

Interacting drugs

Fluoxetine

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07

Biomarkers

SLC6A4 gene polymorphisms (e.g., 5-HTTLPR) (PubMed: 17113158)SERT occupancy measured via PET imaging (e.g., [11C]DASB) (PubMed: 17113158)Platelet serotonin levels (PubMed: 15173104)

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