MOLECULAR CHARACTERIZATION OF THE HUMAN EAA5 (GLUR7) RECEPTOR - A HIGH-AFFINITY KAINATE RECEPTOR WITH NOVEL POTENTIAL RNA EDITING SITES

Several cDNA clones encoding EAA5 receptor polypeptides were isolated from a human fetal brain library. The EAA5 cDNAs demonstrated an 88.7- 90.1% nucleotide identity with rat GluR7 cDNAs. The nucleotide sequenc e of EAA5 would encode a 919-amino acid protein, that has a 97.7-98.9% identity with the rat GluR7 receptor. Two variations of the EAA5 cDNA were identified which result in amino acid substitutions in the predi cted extracellular amino-terminal region; Ser(310) --> Ala and Arg(352 ) --> Gln. These variations can be attributed to RNA editing involving T --> G and G --> A substitutions. Both the location (with respect to glutamate receptors), and the nucleotides involved, in this putative RNA editing are novel and may therefore involve novel mechanisms. Liga nd binding studies with membranes of transfected COS-1 cells expressin g EAA5 polypeptides demonstrate a rank order of ligand affinity simila r to that observed with the rat GluR7 receptor, and a dissociation con stant for kainate (2.72 +/- 0.12 nM (n = 3)) that is approximately 20- to 30-fold higher than that observed for the rat GluR7 receptor. All of the ligands tested had a higher affinity for the human EAA5 recepto r as compared to the rat GluR7 receptor. This report provides another example of pharmacological differences for similar receptors across sp ecies.