Excitatory amino acid transporter 1

Excitatory amino acid transporter 1 (EAAT1), encoded by SLC1A3, is a sodium-dependent, high-affinity transporter that mediates the uptake of L-glutamate, L-aspartate, and D-aspartate from the extracellular space into cells (UniProt: P43003). The protein functions as a symporter, coupling amino acid transport to the movement of multiple sodium and potassium ions, and also mediates chloride flux to prevent charge accumulation. These mechanisms are essential for rapid removal of glutamate from the synaptic cleft, terminating postsynaptic signaling.

EAAT1 is primarily expressed in glial cells and plays a critical role in glutamate homeostasis within the central nervous system. Beyond its physiological function, mutations in SLC1A3 are associated with episodic ataxia 6, a neurological disorder characterized by ataxia, seizures, and migraine (UniProt: P43003).

In Alzheimer's disease, EAAT1 is significantly upregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of +1.54 (Chaparral AD proteomics). This upregulation was detected across subcellular fractions in a TMT-labeled quantitative proteomics experiment, suggesting altered glutamate handling in AD brain that may reflect compensatory glial responses or changes in synaptic glutamate dynamics during neurodegeneration.