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Regulation of NMDA receptors by cyclin-dependent kinase-5. 2001

B S Li, and M K Sun, and L Zhang, and S Takahashi, and W Ma, and L Vinade, and A B Kulkarni, and R O Brady, and H C Pant
Laboratory of Neurochemistry, Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012694 Serine A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids. L-Serine,L Serine
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017774 Long-Term Potentiation A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. Long Term Potentiation,Long-Term Potentiations,Potentiation, Long-Term,Potentiations, Long-Term

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