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 mous e genome. Cloning of the mouse cDNA revealed a protein consisting of 1003 a mino 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 mem bers with a signal peptide and four membrane-associated regions. Amino acid s forming a ligand-binding pocket are conserved. When coexpressed with NR1 and NR2A in heterologous cells, NR3B suppressed glutamate-induced current s imilarly to NR3A. Thus members of the NR3 class of NMDA receptors act as do minant-negative subunits in the NMDA receptor complex. NR3B shows very rest ricted expression in somatic motoneurons of the brainstem and spinal cord. Its expression in other types of motoneurons, including autonomic motoneuro ns in Onuf's nucleus and oculomotor neurons, is significantly weaker. Our r esults indicate that NR3B is important as a regulatory subunit that control s NMDA receptor transmission in motoneurons. It may be involved in the path ogenesis of neurodegenerative diseases involving motoneurons as well.