Calcineurin acts via the C-terminus of NR2A to modulate desensitization of NMDA receptors.
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.
Krupp
Johannes J
JJ
Vollum Institute, Oregon Health & Science University, L474, 3181 SW Sam Jackson Park Rd., Portland OR 97201, USA. johannes.krup@astrazeneca.com
Vissel
Bryce
B
Thomas
Christopher G
CG
Heinemann
Stephen F
SF
Westbrook
Gary L
GL
D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000502:physiology; D006801:Humans; D009154:Mutation / Q000502:physiology; D009942:Organometallic Compounds / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000235:genetics; D014639:Vanadium / Q000494:pharmacology
D019703:Calcineurin; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D005998:Glycine; D009942:Organometallic Compounds; D010618:Phenanthrolines; D017027:Protein Tyrosine Phosphatases; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D012694:Serine; D014639:Vanadium; C120997:NR2A NMDA receptor; C102120:bisperoxo(1,10-phenanthroline)oxovanadate(1-)