Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner

We have identified a novel glutamate receptor subunit on the human and mouse genome. Cloning of the mouse cDNA revealed a protein consisting of 1003 amino acids encoded by at least nine exons. This protein showed the highest similarity (51%) to the NR3A subunit of the NMDA receptor and therefore was termed NR3B. NR3B has a structure typical of glutamate receptor family members with a signal peptide and four membrane-associated regions. Amino acids forming a ligand-binding pocket are conserved. When coexpressed with NR1 and NR2A in heterologous cells, NR3B suppressed glutamate-induced current similarly to NR3A. Thus members of the NR3 class of NMDA receptors act as dominant-negative subunits in the NMDA receptor complex. NR3B shows very restricted expression in somatic motoneurons of the brainstem and spinal cord. Its expression in other types of motoneurons, including autonomic motoneurons in Onuf's nucleus and oculomotor neurons, is significantly weaker. Our results indicate that NR3B is important as a regulatory subunit that controls NMDA receptor transmission in motoneurons. It may be involved in the pathogenesis of neurodegenerative diseases involving motoneurons as well.