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*

*この研究の対応する著者

研究成果: Article査読

78 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)502-512
ページ数11
ジャーナルJournal of neurochemistry
93
2
DOI
出版ステータスPublished - 2005 4月
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 細胞および分子神経科学

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