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

Raymond S Roginski, Farida Goubaeva, Maya Mikami, Emma Fried-Cassorla, Mohan R Nair, Jay Yang

Department of Anesthesiology and Critical Care, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. roginskr@uphs.upenn.edu

Neuroreport 2008 Nov 19

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We hypothesized that proteins from the GRINL1A complex transcription unit called Gcom proteins modulate glutamatergic neurotransmission through interaction with the NR1 subunit of the N-methyl D-aspartate (NMDA) receptor. Cotransfection of hemagglutinin-tagged Gcom1 (GRINL1A combined transcript 1) and NR1 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 GRINL1A proteins and the NMDA receptor. Anti-Gcom1 and anti-NR1 anti bodies revealed colocalization of postsynaptic immunoreactivity in rat cortical and hippocampal neurons. Finally, anti-Gcom1 anti bodies specifically inhibited NMDA excitotoxicity in rat cortical neurons, suggesting a functional interaction of Gcom and NR1 proteins. Our results are consistent with a facilatory role of GRINL1A proteins in glutamatergic signal transduction through interaction with the NMDA receptor.

Citation

Raymond S Roginski, Farida Goubaeva, Maya Mikami, Emma Fried-Cassorla, Mohan R Nair, Jay Yang. GRINL1A colocalizes with N-methyl D-aspartate receptor NR1 subunit and reduces N-methyl D-aspartate toxicity. Neuroreport. 2008 Nov 19;19(17):1721-6