Regulation of NMDA receptors by cyclin-dependent kinase-5.
Members of the N-methyl-d-aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders in the central nervous system. NMDARs are phosphorylated by both serine/threonine and tyrosine kinases. Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.
Li
B S
BS
Laboratory of Neurochemistry, Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Sun
M K
MK
Zhang
L
L
Takahashi
S
S
Ma
W
W
Vinade
L
L
Kulkarni
A B
AB
Brady
R O
RO
Pant
H C
HC
D000818:Animals; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D009435:Synaptic Transmission
C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases