Regulation of NMDA receptors by cyclin-dependent kinase-5

Members of the N-methyl-D-aspartate (NMDA) class of glutamate receptors (NM DARs) are critical for development, synaptic transmission, learning and mem ory; they are targets of pathological disorders in the central nervous syst em. NMDARs are phosphorylated by both serine/threonine and tyrosine kinases . Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates wit h and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells . Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks bo th long-term potentiation induction and NMDA-evoked currents in rat CA1 hip pocampal neurons. These results suggest that Cdk5 plays a key role in synap tic transmission and plasticity through its up-regulation of NMDARs.