GRINL1A colocalizes with N-methyl D-aspartate receptor NR1 subunit and reduces N-methyl D-aspartate toxicity.
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 antibodies revealed colocalization of postsynaptic immunoreactivity in rat cortical and hippocampal neurons. Finally, anti-Gcom1 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.
Department of Anesthesiology and Critical Care, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. roginskr@uphs.upenn.edu
Raymond S
RS
Roginski
Farida
F
Goubaeva
Maya
M
Mikami
Emma
E
Fried-Cassorla
Mohan R
MR
Nair
Jay
J
Yang
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D012319:RNA Polymerase II; D051381:Rats; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014162:Transfection
C409466:NR1 NMDA receptor; C433812:POLR2M protein, human; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D012319:RNA Polymerase II