The cyclin-dependent kinase Cdk5 controls multiple aspects of axon patterning in vivo
The cyclin-dependent kinase Cdk5 controls multiple aspects of axon patterning in vivo
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DOI：
10.1016/s0960-9822(00)00487-5
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发表时间：
2000-05-18
期刊：
影响因子：
9.2
通讯作者：
Giniger, E
中科院分区：
文献类型：
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作者：
Connell-Crowley, L;Le Gall, M;Giniger, E
细胞周期蛋白依赖性激酶 5 (Cdk5) 是 Cdks 亚家族之一，参与控制细胞分化和形态而不是细胞分裂。具体而言，Cdk5 及其激活亚基 p35 与轴突延伸过程中的生长锥运动有关。 Cdk5 和 p35 均在有丝分裂期神经元中表达，并定位于生长锥 [1-4]。 Cdk5-p35 复合物与 Rac GTPase 相互作用，Rac GTPase 是生长锥运动所需的蛋白质 [5]。使用培养神经元的研究表明，Cdk5 活性控制神经突延伸的效率 [3,4]。缺乏p35的突变小鼠表现出微妙的轴突引导缺陷[6]，但这些小鼠在神经元迁移方面存在严重缺陷[6-8]，因此很难准确定义Cdk5-p35复合物在体内的作用。在这里，我们检查了果蝇胚胎中 Cdk5 在轴突模式中的功能。虽然我们的数据支持 Cdk5-p35 参与轴突发生的观点，但不支持 Cdk5 只是促进生长锥运动的观点，相反，我们发现破坏 Cdk5 功能会导致轴突模式普遍错误。
Cyclin-dependent kinase 5 (Cdk5) is one of a subfamily of Cdks involved in the control of cell differentiation and morphology rather than cell division. Specifically, Cdk5 and its activating subunit, p35, have been implicated in growth cone motility during axon extension. Both Cdk5 and p35 are expressed in past-mitotic neurons and are localized to growth cones [1-4]. The Cdk5-p35 complex interacts with the Rac GTPase, a protein required for growth cone motility [5], Studies using cultured neurons have suggested that Cdk5 activity controls the efficiency of neurite extension [3,4]. Mutant mice lacking p35 exhibit subtle axon-guidance defects [6], but these mice have severe defects in neuronal migration [6-8], making it difficult to define precisely the role of the Cdk5-p35 complex in vivo. Here, we examined Cdk5 function in axon patterning In the Drosophila embryo. Although our data support the idea that Cdk5-p35 is involved in axonogenesis, they do not support the view that Cdk5 simply promotes growth cone motility, Instead, we found that disrupting Cdk5 function caused widespread errors in axon patterning.