Current address: Molecular Biology, Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Eastwick Road, Harlow, Essex, CM20
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
Version of Record online: 6 JUN 2002
Journal of Neurochemistry
Volume 81, Issue 6, pages 1298–1307, June 2002
How to Cite
Rutter, A. R., Freeman, F. M. and Stephenson, F. A. (2002), 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. Journal of Neurochemistry, 81: 1298–1307. doi: 10.1046/j.1471-4159.2002.00923.x
Current address: School of Biological Sciences, Biology Department, University of Sussex, Falmer, Brighton BN1 9QG, UK.
- Issue online: 6 JUN 2002
- Version of Record online: 6 JUN 2002
- Received October 25, 2001; revised manuscript received March 7, 2002; accepted March 12, 2002.
- CGP 39653;
- NMDA receptor;
Coexpression of PSD-95c-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 [3H]MK801 binding similar to that previously described for l-glutamate. The inhibition constants (KIs) for the binding of l-glutamate and glycine to NR1-1a/NR2A determined by [3H]CGP 39653 and [3H]MDL 105 519 displacement assays, respectively, were not significantly different between NR1-1a/NR2A receptors coexpressed ± PSD-95c-Myc. The increased EC50 for l-glutamate enhancement of [3H]MK801 binding was also found for NR1-2a/NR2A and NR1-4b/NRA receptors thus the altered EC50 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-95c-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-95c-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.