GRINL1A colocalizes with N-methyl D-aspartate receptor NR1 subunit and reduces N-methyl D-aspartate toxicity.

We hypothesized that proteins from the GRINLIA complex transcription unit called Gcom proteins modulate glutamatergic neurotransmission through interaction with the NRI subunit of the N-methyl D-aspartate (NMDA) receptor. Cotransfection of hemagglutinin-tagged Gcoml (GRINLIA combined transcript I) and NRI cDNAs into HEK293 cells revealed overlapping fluorescent signals in the plasma membrane. Coimmunoprecipitation studies demonstrated reciprocal coimmunoprecipitation from rat brain protein isolates, suggesting an interaction between GRINLIA proteins and the NMDA receptor. Anti-Gcoml and anti-NRI antibodies revealed colocalization of postsynaptic immunoreactivity in rat cortical and hippocampal neurons. Finally, anti-Gcoml antibodies specifically inhibited NMDA excitotoxicity in rat cortical neurons, suggesting a functional interaction of Gcom and NRI proteins. Our results are consistent with a facilatory role of GRINLIA proteins in glutamatergic signal transduction through interaction with the NMDA receptor.