Excitatory amino acid transporter 3 or Excitatory amino acid transporter 4 (EAAT3 / EAAT4)

Excitatory amino acid transporters 3 (EAAT3, SLC1A1) and 4 (EAAT4, SLC1A6) are sodium-dependent, high-affinity glutamate transporters belonging to the solute carrier family 1 (SLC1)[6][7]. EAAT3 is primarily expressed in neurons throughout the CNS, particularly in hippocampus, striatum, and cerebellum, while EAAT4 is predominantly localized to cerebellar Purkinje cells[6][5][1]. Both play essential roles in clearing extracellular glutamate from the synaptic cleft and limiting spillover to extrasynaptic receptors, thereby regulating excitatory neurotransmission and protecting against excitotoxicity[5][3][6]. EAAT3 is also unique in its efficient transport of L-cysteine, supporting glutathione synthesis and redox balance[2]. Loss-of-function mutations in EAAT3 cause dicarboxylic aminoaciduria, while dysfunction or altered expression of EAAT3/EAAT4 is implicated in neurodegenerative and psychiatric diseases[4][6]. Both transporters operate as trimeric complexes with characteristic transmembrane topology and may also exhibit anion channel activity[1][5][7].

Other names

EAAT3 (also known as EAAC1, SLC1A1)EAAT4 (also known as SLC1A6)

Increased transporter expression or function reduces extracellular glutamate and protects from excitotoxicity; blockade or mutation impairs glutamate uptake and increases synaptic glutamate[4][6]