Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation.
Nat Neurosci
; 10(7): 880-886, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17529984
ABSTRACT
Learning is accompanied by modulation of postsynaptic signal transduction pathways in neurons. Although the neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) has been implicated in cognitive disorders, its role in learning has been obscured by the perinatal lethality of constitutive knockout mice. Here we report that conditional knockout of Cdk5 in the adult mouse brain improved performance in spatial learning tasks and enhanced hippocampal long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents. Enhanced synaptic plasticity in Cdk5 knockout mice was attributed to reduced NR2B degradation, which caused elevations in total, surface and synaptic NR2B subunit levels and current through NR2B-containing NMDARs. Cdk5 facilitated the degradation of NR2B by directly interacting with both it and its protease, calpain. These findings reveal a previously unknown mechanism by which Cdk5 facilitates calpain-mediated proteolysis of NR2B and may control synaptic plasticity and learning.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Receptores de N-Metil-D-Aspartato
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Quinase 5 Dependente de Ciclina
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Aprendizagem
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Plasticidade Neuronal
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article