EAAC1

EAAC1, short for excitatory amino acid carrier 1, is a neuronal excitatory amino acid transporter encoded by the SLC1A1 gene in humans. It is part of the SLC1 family of Na+-dependent transporters and is commonly referred to as EAAT3 in the literature. EAAC1 is broadly expressed in the brain, with notable presence in neurons of the cortex and hippocampus, and shows lower levels in other tissues.

The primary function of EAAC1 is to remove excitatory amino acids, especially glutamate, from the synaptic cleft, contributing to termination of excitatory neurotransmission and providing neurons with amino acids for metabolic needs. The transporter operates via a Na+-dependent mechanism and is coupled to proton gradients, with a potassium counter-transport step helping to reset the transporter after substrate uptake. This activity helps regulate extracellular glutamate concentrations and supports neuronal metabolism.

Regulation and localization of EAAC1 involve trafficking between intracellular stores and the plasma membrane. Its surface expression is modulated by neuronal activity and signaling pathways, including phosphorylation and interactions with scaffolding and trafficking proteins, which influence transporter availability at synapses.

Clinical significance: Variants and alterations in SLC1A1/EAAC1 have been studied in relation to neuropsychiatric and neurological conditions, most notably obsessive-compulsive disorder in various populations. Findings are mixed, and associations are not yet fully resolved, but disrupted EAAC1 function can affect glutamate homeostasis and neuronal metabolism, with potential impacts on neural circuit function. See also: other excitatory amino acid transporters in the SLC1 family.