Calcineurin acts via the C-terminus of NR2A to modulate desensitization of NMDA receptors

Neuropharmacology. 2002 Apr;42(5):593-602. doi: 10.1016/s0028-3908(02)00031-x.

Abstract

Phosphatase IIb (calcineurin, CaN) can reduce N-methyl-D-aspartate (NMDA) synaptic responses by enhancing glycine-independent desensitization. We examined the action of CaN on desensitization in recombinant NMDA receptors comprised of NMDA receptor 1 (NR1) and NR2A subunits. The C-terminus of NR2A, but not NR1, was critical for modulation of desensitization by CaN. Alanine-scanning mutagenesis indicated that serines 900 and 929 in NR2A altered desensitization, as did inhibition of tyrosine phosphatases. Our data suggest that dephosphorylation-dependent regulation of the C-terminus of NR2A increases desensitization of NMDA receptors, providing an additional mechanism for modulation of synaptic signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcineurin / metabolism
  • Calcineurin Inhibitors*
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Glycine / physiology
  • Humans
  • Mutation / physiology
  • Organometallic Compounds / pharmacology
  • Phenanthrolines / pharmacology
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Recombinant Proteins / metabolism
  • Serine / genetics
  • Vanadium / pharmacology

Substances

  • Calcineurin Inhibitors
  • Enzyme Inhibitors
  • NMDA receptor A1
  • NR2A NMDA receptor
  • Organometallic Compounds
  • Phenanthrolines
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Vanadium
  • Serine
  • bisperoxo(1,10-phenanthroline)oxovanadate(1-)
  • Calcineurin
  • Protein Tyrosine Phosphatases
  • Glycine