ALTERNATIVELY SPLICED ISOFORMS OF THE NMDARI RECEPTOR SUBUNIT

Molecularly diverse forms of the NMDA-receptor subunit NR I are formed by alternative RNA splicing. Differential splicing of three exons gen erates as many as eight NR1 splice variants, seven of which have been identified in cDNA libraries. The alternatively spliced exons encode a 21 amino acid sequence in the N-terminus domain (termed N1), and adja cent sequences of 37 and 38 amino acids in the C-terminus domain (term ed C1 and C2, respectively). Splicing out the exon segment that encode s the C2 cassette removes the first stop codon, resulting in a new ope n reading frame that encodes an unrelated sequence of 22 amino acids ( C2') before a second stop codon is reached. Differential RNA splicing alters the structural, physiological and pharmacological properties of receptors that comprise NR1 subunits. Diversity of NMDA receptors is also caused by differential association with members of the NR1 gene f amily. The finding of cell-specific expression and developmental regul ation of NR1 splice variants, and of the NR2 subunits, provides an exp lanation for the diversity of properties of NMDA receptors in differen t neuronal populations.