Control of cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability

Academic Article


  • Although the roles of cyclin-dependent kinase 5 (Cdk5) in neurodevelopment and neurodegeneration have been studied extensively, regulation of Cdk5 activity has remained largely unexplored. We report here that glutamate, acting via NMDA or kainate receptors, can induce a transient Ca 2+/ calmodulin-dependent activation of Cdk5 that results in enhanced autophosphorylation and proteasome-dependent degradation of a Cdk5 activator p35, and thus ultimately down-regulation of Cdk5 activity. The relevance of this regulation to synaptic plasticity was examined in hippocampal slices using theta burst stimulation. p35 -/- mice exhibited a lower threshold for induction of long-term potentiation. Thus excitatory glutamatergic neurotransmission regulates Cdk5 activity through p35 degradation, and this pathway may contribute to plasticity. © 2005 International Society for Neurochemistry.
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    Author List

  • Wei FY; Tomizawa K; Ohshima T; Asada A; Saito T; Nguyen C; Bibb JA; Ishiguro K; Kulkarni AB; Pant HC
  • Start Page

  • 502
  • End Page

  • 512
  • Volume

  • 93
  • Issue

  • 2