Xie Zhigang, Samuels Benjamin Adam, Tsai Li-Huei
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cereb Cortex. 2006 Jul;16 Suppl 1:i64-8. doi: 10.1093/cercor/bhj170.
Migration of neurons to their proper position underlies mammalian brain development. To remain on the proper path, a migrating neuron needs to detect various external signals and respond by efficiently remodeling its cytoskeleton. Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, regulates neuronal migration by phosphorylating a number of intracellular substrates. Deficiencies in Cdk5 preferentially cause impairments in radial glia-guided migration, a process that involves complex remodeling of the cytoskeleton, particularly the microtubules. Furthermore, the defined substrates of Cdk5 that are important for migration generally link Cdk5 to the cytoskeleton. Interestingly, none of these phosphorylation events seem to directly control the activity of the substrates. Taken together, these findings support a model in which Cdk5 does not directly control the detection of any specific external signals but instead regulates efficient remodeling of the cytoskeleton through phosphorylation of multiple substrates.
神经元迁移到其适当位置是哺乳动物大脑发育的基础。为了保持在正确的路径上，迁移中的神经元需要检测各种外部信号，并通过有效地重塑其细胞骨架做出反应。细胞周期蛋白依赖性激酶5（Cdk5）是细胞周期蛋白依赖性激酶家族的成员，通过磷酸化许多细胞内底物来调节神经元迁移。Cdk5的缺陷优先导致放射状胶质细胞引导的迁移受损，这一过程涉及细胞骨架，特别是微管的复杂重塑。此外，对迁移重要的Cdk5特定底物通常将Cdk5与细胞骨架联系起来。有趣的是，这些磷酸化事件似乎都没有直接控制底物的活性。综上所述，这些发现支持了一个模型，即Cdk5并不直接控制任何特定外部信号的检测，而是通过多种底物的磷酸化来调节细胞骨架的有效重塑。
