Regulation of NMDA receptors by cyclin-dependent kinase-5

AUTOR(ES)

Li, Bing-Sheng

FONTE

The National Academy of Sciences

RESUMO

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.

Documentos Relacionados

• Regulation of cyclin-dependent kinase 5 and casein kinase 1 by metabotropic glutamate receptors
• Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation
• Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses
• Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3
• Mechanisms of Cyclin-Dependent Kinase Inactivation by Progestins