SERT Protein, Human (HEK293, Strep)

SERT is a serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton, forming an overall electroneutral transport cycle. It mediates serotonin uptake from the extracellular space into the cytosol, thereby limiting intercellular serotonin signaling. SERT is essential for serotonin homeostasis in the central nervous system: during somatosensory cortex development, it acts in glutamatergic neurons to regulate serotonin uptake and its trophic functions, ensuring proper spatial organization of cortical neurons and sensory circuit formation; in the mature cortex, it primarily functions in brainstem raphe neurons to reuptake serotonin from the synaptic cleft into presynaptic terminals, terminating synaptic serotonin signaling (By similarity). In the gastrointestinal tract, SERT modulates mucosal serotonin levels via uptake and clearance in enterocytes, playing a critical role in enteric neurogenesis and gastrointestinal reflexes (By similarity). It also regulates blood serotonin levels by facilitating rapid high-affinity uptake of plasma serotonin into platelets, where it is stored in dense granules via vesicular monoamine transporters and released upon stimulation. Mechanistically, the transport cycle initiates with an outward-open conformation bound to Na1(+) and Cl(-). Binding of extracellular Na2(+) and serotonin triggers conformational transitions (outward-occluded→inward-occluded→inward-open), releasing Na2(+) and serotonin into the cytosol. Intracellular K(+) binding drives transitions back (inward-occluded→outward-open), completing the cycle by releasing K(+) (possibly with a proton bound to Asp-98) extracellularly, while Na1(+) and Cl(-) remain bound throughout. Additionally, SERT exhibits serotonin-induced channel-like conductance for monovalent cations (mainly Na(+)), uncoupled from transport, which may influence resting membrane potential or excitability (By similarity).