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


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.


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@article{Wei2005ControlOC, title={Control of cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability.}, author={Fan-Yan Wei and Kazuhito Tomizawa and Toshio Ohshima and Akiko Asada and Taro L. Saito and Chan D K Nguyen and James Bibb and Koichi Ishiguro and Ashok Kulkarni and Harish C. Pant and Katsuhiko Mikoshiba and Hideki Matsui and Shin-ichi Hisanaga}, journal={Journal of neurochemistry}, year={2005}, volume={93 2}, pages={502-12} }