EAATTransporter

EAATTransporter refers to a family of excitatory amino acid transporters that remove glutamate from the extracellular space, including the synaptic cleft, to terminate excitatory signaling and protect neurons from excitotoxic damage. These transporters play a central role in regulating brain glutamate levels and shaping synaptic plasticity.

In vertebrates, five subtypes are recognized: EAAT1 (SLC1A2 or SLC1A3 depending on nomenclature), EAAT2, EAAT3, EAAT4, and EAAT5. They are high-affinity, sodium-dependent transporters that typically function as oligomeric trimers in the plasma membrane. Each subunit features two transmembrane segments and a re-entrant loop, and the proteins operate via an alternating-access mechanism that moves glutamate between outward- and inward-facing states.

Mechanistically, glutamate uptake by EAATs is coupled to the electrochemical gradients of ions. The transport cycle generally involves co-transport of three Na+ ions and one H+ with one molecule of glutamate into the cell, accompanied by the counter-transport of one K+ ion out of the cell. This coupling enables uptake against the glutamate concentration gradient but makes transport sensitive to intracellular and extracellular ion conditions.

Distribution and function vary by subtype. EAAT1 and EAAT2 are abundant in astrocytes and are responsible for most extracellular glutamate clearance in the CNS. EAAT3 is primarily neuronal and contributes to cellular glutamate supply for metabolism and neurotransmission. EAAT4 is mainly cerebellar, and EAAT5 is prominent in the retina. Beyond clearance, EAATs influence synaptic and extrasynaptic signaling and participate in neuronal metabolism.

Clinical relevance includes associations with neurodegenerative diseases, stroke, and epilepsy. Reduced EAAT2 function, for example, has been linked to excitotoxic vulnerability, while enhancing EAAT activity is explored as a therapeutic strategy to limit glutamate-mediated injury.