title: Control of cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Minami-osawa, Hachiohji, Tokyo, Japan.
authors.forename: Fan-Yan
authors.initials: FY
authors.lastname: Wei
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
authors.forename: Akiko
authors.initials: A
authors.lastname: Asada
authors.forename: Taro
authors.initials: T
authors.lastname: Saito
authors.forename: Chan
authors.initials: C
authors.lastname: Nguyen
authors.forename: James A
authors.initials: JA
authors.lastname: Bibb
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: Harish C
authors.initials: HC
authors.lastname: Pant
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsui
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hisanaga
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*
chemical_list: C492236:Cdk5r1 protein, mouse; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases