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

Fan Yan Wei, Kazuhito Tomizawa, Toshio Ohshima, Akiko Asada, Taro Saito, Chan Nguyen, James A. Bibb, Koichi Ishiguro, Ashok B. Kulkarni, Harish C. Pant, Katsuhiko Mikoshiba, Hideki Matsui, Shin Ichi Hisanaga

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)502-512
Number of pages11
JournalJournal of Neurochemistry
Issue number2
StatePublished - Apr 2005


  • Calmodulin
  • Cyclin-dependent kinase 5
  • Glutamate
  • Long-term potentiation
  • N-methyl-D-aspartate
  • Proteasome

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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