EAAT

EAAT, short for excitatory amino acid transporter, refers to a family of high-affinity membrane transporters that clear glutamate (and to a lesser extent aspartate) from the synaptic cleft in the central nervous system. The EAAT family is part of the SLC1 gene family and includes five members: EAAT1 (GLAST, SLC1A3), EAAT2 (GLT-1, SLC1A2), EAAT3 (EAAC1, SLC1A1), EAAT4 (SLC1A6), and EAAT5 (SLC1A7).

Expression patterns vary by subtype. EAAT1 and EAAT2 are predominantly expressed in astrocytes, EAAT3 is mainly neuronal, EAAT4 is found in cerebellar Purkinje cells, and EAAT5 is present in the retina. Functionally, EAATs are co-transporters that use the Na+ and H+ electrochemical gradients to move glutamate into cells while counter-transporting K+. The typical stoichiometry involves the co-transport of three Na+ and one H+ with one glutamate and the counter-transport of one K+. In addition to transport, several EAATs exhibit an anion conductance activated by substrate binding, adding to their functional repertoire.

Physiologically, EAATs terminate excitatory signaling and protect neurons from glutamate-induced excitotoxicity. Dysregulation or loss of EAAT function has been linked to various neurological conditions, including ALS, ischemia, epilepsy, and neurodegenerative diseases. EAAT2, in particular, is a major determinant of extracellular glutamate levels, and increasing its expression or activity is an area of therapeutic research. Structurally, EAATs are believed to form homotrimers with each protomer capable of independent transport.