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

被引：80

作者：

Wei, FY

Tomizawa, K

Ohshima, T

Asada, A

Saito, T

Nguyen, C

Bibb, JA

Ishiguro, K

Kulkarni, AB

Pant, HC

Mikoshiba, K

Matsui, H

Hisanaga, S ^{[1
]}

机构：

[1] Tokyo Metropolitan Univ, Grad Sch Sci, Dept Sci Biol, Hachioji, Tokyo 1920397, Japan

[2] Okayama Univ, Grad Sch Med & Dent, Dept Physiol, Okayama, Japan

[3] Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama, Japan

[4] Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA

[5] Mitsubishi Kagaku Inst Life Sci, Tokyo, Japan

[6] NINDS, Funct Genom Unit, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA

[7] NINDS, Lab Neurochem, NIH, Bethesda, MD USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2005年 / 93卷 / 02期

关键词：

calmodulin; cyclin-dependent kinase 5; proteasome; glutamate; N-methyl-D-aspartate; long-term potentiation;

D O I：

10.1111/j.1471-4159.2005.03058.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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 Ca2+/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.

引用

页码：502 / 512

页数：11

共 51 条

[1]

Cyclin-dependent kinase 5 (cdk5) activation requires interaction with three domains of p35 [J].