Excitatory amino acid transporter 3 (EAAT3)

Excitatory amino acid transporter 3 (EAAT3), encoded by the *SLC1A1* gene, is a major neuronal high-affinity sodium-dependent glutamate transporter found predominately in the plasma membrane of neurons[1][3][5][7][9]. EAAT3 is essential for clearing extracellular glutamate and terminating the postsynaptic effect of glutamate neurotransmission, thereby preventing neurotoxicity caused by excessive glutamate[3][4][5]. It is also the principal transporter for neuronal cysteine uptake, which is crucial for the synthesis of glutathione, a major antioxidant in neurons[1][3][5]. Loss or inhibition of EAAT3 leads to reduced antioxidant capacity, increased oxidative stress, and age-dependent neuronal loss[1][3]. EAAT3 interacts with various proteins (such as GTRAP3-18), and its function can be negatively regulated by alternative splicing and interacting proteins, adding complexity to its regulation[2][7]. Pathological changes in EAAT3 expression or function have been associated with several neurological and psychiatric diseases—including schizophrenia, epilepsy, multiple sclerosis, and obsessive-compulsive disorder—often through mechanisms involving glutamate excitotoxicity or impaired antioxidant defense[1][7][8][10]. EAAT3 may also have roles in cancer due to altered cysteine metabolism[8]. Experimental drugs/interventions that inhibit EAAT3 (such as DL-TBOA) demonstrate the importance of EAAT3 in maintaining neuronal health and function[2][3].

Other names

SLC1A1EAAC1Excitatory amino acid carrier 1Neuronal and epithelial glutamate transporterSodium-dependent glutamate/aspartate transporter 3Solute carrier family 1 member 1hEAAC1DCBXASCZD18HEAAC1

Inhibition of glutamate transport, Negative modulation via protein interaction (e.g., GTRAP3-18), Reduced cysteine/glutathione synthesis when inhibited