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

Johannes J. Krupp, Bryce Vissel, Christopher G. Thomas, Stephen F. Heinemann, Gary L. Westbrook

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)593-602
Number of pages10
JournalNeuropharmacology
Volume42
Issue number5
DOIs
StatePublished - 2002

Keywords

  • Calcineurin
  • Desensitization
  • Mutagenesis
  • NMDA receptors
  • Patch-clamp
  • Tyrosine phosphatases

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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