Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice.
Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice.
复制标题
α 原钙粘蛋白和 Pyk2 激酶通过 Rac1 GTPase 和 WAVE 复合物调节小鼠皮质神经元迁移和细胞骨架动力学
作者：
Fan L;Lu Y;Shen X;Shao H;Suo L;Wu Q
不同的簇状原钙粘附素被认为在大脑中的轴突形态发生和神经元连接中发挥作用。在这里，我们报道了原钙粘蛋白α(Pcdha)基因簇通过WAVE(Wiskott-Aldrich综合征家族Verprolin同源蛋白，也称为WASF)复合体来调节皮质发育过程中神经元的迁移和原代皮质培养中的细胞骨架动力学。此外，Pcdhβ下游的非受体细胞黏附蛋白和支架蛋白PYK2(PYK2，也被称为PTK2B、CAKα、RAFTK、FAK2和CADTK)的过表达通过使小GTP酶RAC1失活来损害皮质神经元的迁移。因此，我们定义了一个分子α/WAVE/PYK2/RAC1轴，从原钙粘蛋白细胞表面受体到肌动蛋白细胞骨架动力学，在小鼠大脑皮质神经元迁移和树突形态发生中。
Diverse clustered protocadherins are thought to function in neurite morphogenesis and neuronal connectivity in the brain. Here, we report that the protocadherin alpha (Pcdha) gene cluster regulates neuronal migration during cortical development and cytoskeletal dynamics in primary cortical culture through the WAVE (Wiskott-Aldrich syndrome family verprolin homologous protein, also known as Wasf) complex. In addition, overexpression of proline-rich tyrosine kinase 2 (Pyk2, also known as Ptk2b, Cakβ, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdhα, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Thus, we define a molecular Pcdhα/WAVE/Pyk2/Rac1 axis from protocadherin cell-surface receptors to actin cytoskeletal dynamics in cortical neuron migration and dendrite morphogenesis in mouse brain.