Molecular biology of the Apteronotus NMDA receptor NR1 subunit

The complete sequences and expression patterns of the NR1 (aptNR1) subunit of the N-methyl-D-aspartate (NMDA) receptor and its alternative splice isoforms have been determined for the weakly electric fish Apteronotus leptorhynchus. The deduced amino acid sequence of aptNR1 is approximately 88% identical to the NR1 sequences of other vertebrate. Two of the three alternative splice cassettes previously described for mammalian NR1s, N1 and C1, are present in aptNR1, but the third cassette, C2, is not found. In addition, two teleost-specific splice cassettes occur on the N-terminal side of the C1 sequence. The cellular patterns of aptNR1 expression, including the patterns of N1 and C1 splicing, have been mapped using the in situ hybridization technique. High levels of aptNR1 mRNA were detected throughout the central nervous system including most neurons of the electrosensory system, with the highest levels in electrosensory lateral line lobe pyramidal cells. Expression of the N1 splice isoform was higher in more caudal regions of the brain, and expression of the C1 splice isoform was higher in more rostral regions. The N1 splice isoform was present in almost all NR1-positive cells, in contrast to the C1 splice isoform which was restricted to a subset of NR1-positive cells. These results demonstrate that the NR1 subunit of the NMDA receptor is evolutionarily conserved across species and that regulation of alternative RNA splicing modulates the properties of NR1 in different neurons of the central nervous system of A. leptorhynchus.