Glycine-independent NMDA receptor desensitization: localization of structural determinants

Neuron. 1998 Feb;20(2):329-39. doi: 10.1016/s0896-6273(00)80460-2.


In studying chimeras of NR2A and NR2C subunits of the NMDA receptor, we have found that glycine-independent desensitization depends on two regions of the extracellular N-terminal domain. One corresponds to a stretch of approximately 190 amino acids preceding the glutamate-binding domain S1. The other localizes at the interface between the N-terminal segment and the first transmembrane domain of NR2A subunits and involves A555 and S556. Both regions support desensitization in the absence of the other with different time courses. Desensitization did not develop with time in receptors containing the entire N-terminal region of NR2C. The introduction of A555 into the corresponding position of NR2C subunits enabled the receptors to manifest time-dependent increase in desensitization. Thus, this determinant behaves as an allosteric effector for glycine-independent desensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Chelating Agents / pharmacology
  • Chimera
  • Egtazic Acid / pharmacology
  • Glycine / pharmacology*
  • Hippocampus / cytology
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Kidney / cytology
  • Kinetics
  • Neurons / chemistry
  • Protein Structure, Tertiary
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Sensitivity and Specificity
  • Transfection


  • Chelating Agents
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Egtazic Acid
  • Glycine