PMID- 12068077 OWN - NLM STAT- MEDLINE DCOM- 20020712 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 81 IP - 6 DP - 2002 Jun TI - Further characterization of the molecular interaction between PSD-95 and NMDA receptors: the effect of the NR1 splice variant and evidence for modulation of channel gating. PG - 1298-307 AB - Coexpression of PSD-95(c-Myc) with NR1-1a/NR2A NMDA receptors in human embryonic kidney (HEK) 293 cells resulted in a decrease in efficacy for the glycine stimulation of [3 H]MK801 binding similar to that previously described for l-glutamate. The inhibition constants (K (I) s) for the binding of l-glutamate and glycine to NR1-1a/NR2A determined by [3 H]CGP 39653 and [3 H]MDL 105 519 displacement assays, respectively, were not significantly different between NR1-1a/NR2A receptors coexpressed +/- PSD-95(c-Myc). The increased EC(50) for l-glutamate enhancement of [3 H]MK801 binding was also found for NR1-2a/NR2A and NR1-4b/NRA receptors thus the altered EC(50) is not dependent on the N1, C1 or C2 exon of the NR1 subunit. The NR1-4b but not the NR1-1a subunit was expressed efficiently at the cell surface in the absence of NR2 subunits. Total NR1-4b and NR1-4b/NR2A expression was enhanced by PSD-95(c-Myc) but whole cell enzyme-linked immunoadsorbent assays (ELISAs) showed that this increase was not due to increased expression at the cell surface. It is suggested that PSD-95(c-Myc) has a dual effect on NMDA receptors expressed in mammalian cells, a reduction in channel gating and an enhanced expression of NMDA receptor subunits containing C-terminal E(T/S)XV PSD-95 binding motifs. FAU - Rutter, A Richard AU - Rutter AR AD - Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, London, UK. FAU - Freeman, Fiona M AU - Freeman FM FAU - Stephenson, F Anne AU - Stephenson FA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (DNA, Recombinant) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (NR1 NMDA receptor) RN - 0 (NR2A NMDA receptor) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (postsynaptic density proteins) RN - 132472-31-2 (CGP 39653) RN - 3KX376GY7L (Glutamic Acid) RN - 6LR8C1B66Q (Dizocilpine Maleate) RN - 76726-92-6 (2-Amino-5-phosphonovalerate) RN - TE7660XO1C (Glycine) SB - IM MH - 2-Amino-5-phosphonovalerate/*analogs & derivatives/metabolism MH - Binding, Competitive MH - Cell Line MH - *DNA, Recombinant MH - Dizocilpine Maleate/metabolism MH - Excitatory Amino Acid Antagonists/metabolism MH - Genetic Variation/*physiology MH - Glutamic Acid/metabolism MH - Glycine/pharmacology MH - Humans MH - Ion Channel Gating/*physiology MH - Nerve Tissue Proteins/pharmacology/*physiology MH - Prosencephalon/metabolism MH - Receptors, N-Methyl-D-Aspartate/genetics/metabolism/*physiology EDAT- 2002/06/18 10:00 MHDA- 2002/07/13 10:01 CRDT- 2002/06/18 10:00 PHST- 2002/06/18 10:00 [pubmed] PHST- 2002/07/13 10:01 [medline] PHST- 2002/06/18 10:00 [entrez] AID - 10.1046/j.1471-4159.2002.00923.x [doi] PST - ppublish SO - J Neurochem. 2002 Jun;81(6):1298-307. doi: 10.1046/j.1471-4159.2002.00923.x.