SLC6A4
SLC6A4, also known as 5-HTT, SERT1, HTT and OCD1, is the sodium-dependent serotonin transporter. It takes serotonin up across the plasma membrane into cells, which limits serotonin signalling and supports serotonin homeostasis in the central nervous system. Browse Assay Genie's current range of SLC6A4 research reagents below, or read on for the biology behind the target.
SLC6A4 is an integral membrane protein that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion, and possibly one proton, in an overall electroneutral cycle. By moving serotonin from the extracellular compartment into the cytosol, it limits serotonin intercellular signalling. In the mature cortex it acts mainly in brainstem raphe neurons, taking serotonin from the synaptic cleft back into the presynaptic terminal and so terminating signalling at the synapse. The transporter cycles through outward-open, outward-occluded, inward-occluded and inward-open conformations, with Na(+) and Cl(-) ions bound at defined sites. It also shows serotonin-induced, channel-like conductance for monovalent cations, mainly Na(+), which is uncoupled from the transport cycle and may contribute to resting potential or excitability.
Beyond the synapse, SLC6A4 has several physiological roles. In the developing somatosensory cortex it acts in glutamatergic neurons to control serotonin uptake and its trophic functions, which supports the spatial organisation of cortical neurons and the elaboration of sensory circuits. In the gastrointestinal tract it modulates mucosal serotonin through uptake and clearance in enterocytes, and it is required for enteric neurogenesis and gastrointestinal reflexes. It also sets blood serotonin levels by driving rapid, high-affinity uptake from plasma into platelets, where serotonin is stored in dense granules by vesicular monoamine transporters. UniProt lists the protein at the cell membrane, endosome membrane, synapse, focal adhesions and neuron projections.
The SLC6A4 gene belongs to the solute carrier family 6 and the sodium:neurotransmitter symporter family. Earlier names include 5-hydroxytryptamine (serotonin) transporter and obsessive-compulsive disorder 1. The protein is a target of psychomotor stimulants such as amphetamines and cocaine. A repeat length polymorphism in the gene promoter affects the rate of serotonin uptake, although reports on its possible effect on behaviour and depression conflict. Mouse and rat orthologs are both named Slc6a4.
SLC6A4 terminates serotonin signalling at the synapse by reuptake into presynaptic terminals, making it central to studies of serotonergic neurotransmission.
In developing cortex, SLC6A4-mediated serotonin uptake in glutamatergic neurons supports the organisation of cortical neurons and sensory circuits.
SLC6A4 clears serotonin in enterocytes and is required for enteric neurogenesis and gastrointestinal reflexes, linking it to gut serotonin studies.
A promoter repeat polymorphism alters serotonin uptake, and the transporter is a target of amphetamines and cocaine, so it features in behaviour and drug-action research.
SLC6A4 is a sodium-dependent serotonin transporter. It moves serotonin across the plasma membrane into the cytosol, cotransporting one Na(+) ion in exchange for one K(+) ion. This ends serotonin signalling at synapses, and it also regulates gut mucosal and blood serotonin levels.
SLC6A4 is also called 5-HTT, SERT1, HTT and OCD1. Earlier names include 5-hydroxytryptamine (serotonin) transporter and solute carrier family 6 (neurotransmitter transporter, serotonin), member 4. The protein is catalogued by UniProt as sodium-dependent serotonin transporter.
Mouse and rat both have an ortholog named Slc6a4, so the gene is conserved in common rodent models; check the datasheet of any product for its validated reactivity. A promoter repeat polymorphism affects serotonin uptake, but links to behaviour and depression remain conflicting.
Other solute carriers, vesicular monoamine transporters and neurotransmitter transporters with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P31645; product specifications from Assay Genie datasheets.