The distal carboxyl terminal of rat NR3B subunit regulates NR1-1a/NR3B and NR1-2a/NR3B surface trafficking.

N-Methyl-d-aspartate (NMDA) receptors are multi-subunit receptors formed from assembly of NR1 with NR2 and/or NR3 subunits. In this study, we investigated the role of a conserved RERLR motif present in a region within the distal carboxyl terminal of rat NR3B (between residues 952 and 984) in targeting NR1-1a/NR3B and NR1-2a/NR3B receptors to the cell surface. Surface biotinylation, confocal immunofluorescence microscopy and site-directed mutagenesis studies showed RERLR motif does not influence the surface expression of NR1-1a/NR3B NMDA receptor complex. Our bioinformatics analysis further showed this region can also exist as a coiled-coil domain. Truncation of this putative coiled-coil domain in NR3B affects surface expression of NR1-1a/NR3B and NR1-2a/NR3B receptors similarly suggesting that NR1 C1 cassette is not involved in the effect mediated by the distal carboxyl region of NR3B. This study represents the first attempt to evaluate a specific motif in regulating rat NR3B surface expression.