Excitatory amino acid transporter 3 (EAAT3) (EAAT3)

Excitatory amino acid transporter 3 (EAAT3), encoded by SLC1A1, is a neuronal and epithelial high-affinity glutamate transporter expressed on dendrites and axon terminals that clears synaptic glutamate, transports aspartate, and uniquely among EAATs efficiently transports L-cysteine to support glutathione synthesis and protect against oxidative stress. It is a homotrimeric membrane transporter operating by an elevator mechanism that symports glutamate with three sodium ions and a proton and counter-transports potassium, with well-resolved cryo-EM structures detailing its outward-, intermediate-, and inward-facing conformations and ion/substrate coupling. Dysfunction or genetic variation in SLC1A1 is linked to dicarboxylic aminoaciduria, oxidative-stress–related neuronal loss, and associations with obsessive–compulsive disorder, and EAAT3 has emerging relevance in cancer biology.

Other names

Solute carrier family 1 member 1 (SLC1A1)EAAC1 (historical/neuronal EAAT3 designation in literature; inferred from SLC1A1/EAAT nomenclature; commonly used but not explicitly stated in retrieved pages — inference)

Substrate transporters/inhibitors would modulate glutamate/aspartate/cysteine uptake by altering the coupled symport cycle that moves glutamate with 3 Na+ and 1 H+ and exchanges 1 K+ via an elevator mechanism. Substrate-specific interactions: EAAT3 uniquely transports L-cysteine efficiently, recognizing it in thiolate form via key binding-site residues (D444, R447, N451); molecules affecting these interactions can change uptake and redox homeostasis.