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

作者：Roginski Raymond S^*; Goubaeva Farida; Mikami Maya; Fried Cassorla Emma; Nair Mohan R; Yang Jay

来源：NeuroReport, 2008, 19(17): 1721-1726.

DOI：10.1097/WNR.0b013e328317f05f

• complex transcription unit
• excitotoxicity
• GRINL1A combined transcript 1
• Gdown1
• neuroprotection
• NR1 subunit

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 Gcoml (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-Gcoml and anti-NR1 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 NR1 proteins. Our results are consistent with a facilatory role of GRINL1A proteins in glutamatergic signal transduction through interaction with the NMDA receptor.

• 出版日期2008-11-19