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Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12742-7. Epub 2001 Oct 2.

Regulation of NMDA receptors by cyclin-dependent kinase-5.

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  • 1Laboratory of Neurochemistry, Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

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.

Comment in

  • Telling tails. [Proc Natl Acad Sci U S A. 2001]
PMID:
11675505
[PubMed - indexed for MEDLINE]
PMCID:
PMC60124
Free PMC Article

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