Control of cyclin‐dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability
Control of cyclin‐dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability
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DOI：
10.1111/j.1471-4159.2005.03058.x
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发表时间：
2005-04
影响因子：
4.7
通讯作者：
Fan-Yan Wei;K. Tomizawa;T. Ohshima;A. Asada;Taro Saito;C. Nguyen;J. Bibb;K. Ishiguro;Ashok B Kulkarni;H. Pant;K. Mikoshiba;H. Matsui;S. Hisanaga
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文献类型：
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作者：
Fan-Yan Wei;K. Tomizawa;T. Ohshima;A. Asada;Taro Saito;C. Nguyen;J. Bibb;K. Ishiguro;Ashok B Kulkarni;H. Pant;K. Mikoshiba;H. Matsui;S. Hisanaga
虽然细胞周期蛋白依赖性激酶5（Cdk 5）在神经发育和神经退行性变中的作用已被广泛研究，但Cdk 5活性的调节仍在很大程度上未被探索。我们在此报告，谷氨酸通过NMDA或红藻氨酸受体起作用，可以诱导Cdk 5的瞬时Ca 2 +/钙调蛋白依赖性激活，导致Cdk 5激活剂p35的自磷酸化和蛋白酶体依赖性降解增强，从而最终下调Cdk 5活性。这种调节突触可塑性的相关性进行了研究，在海马切片使用θ爆发刺激。p35-/-小鼠表现出较低的长时程增强诱导阈值。因此，兴奋性突触能神经传递通过p35降解调节Cdk 5活性，并且该通路可能有助于可塑性。
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.