Function of the armadillo protein p0071 in Rho signalling

我们最近发现了一种令人惊讶的新功能，那就是螳螂蛋白p0071。与其相对的p120ctn不同，p0071是细胞分裂所必需的。P0071基因的下调和过表达都干扰了细胞的正常生长和存活，原因是胞质分裂缺陷，导致多核细胞的形成和诱导细胞凋亡。胞质分裂依赖于细胞骨架的重组，导致收缩环的形成。Rho-GTP酶家族的成员是这一过程的重要调节者。胞质分裂对p0071表达改变的反应失败与Rho活性的解除调节有关。在中体，p0071与活性的RhoA以及胞质分裂中必不可少的一种Rho-鸟嘌呤核苷酸交换因子ECT2直接相关。P0071与ECT2共同刺激RhoA交换活性。尽管我们的发现支持p0071在胞质分裂过程中调节空间受限的Rho信号中的重要作用，但它在收缩环上的确切功能以及它在其他细胞环境中的Rho信号功能仍然不清楚。因此，我们计划研究p0071在Rho信号的局部控制中的作用：(1)在胞质分裂过程中收缩环的形成；(2)在上皮细胞极性和上皮-间充质转变中；(3)在轴突生长、收缩和分支中。

We have recently discovered a surprising new function of the armadillo protein p0071. Unlike its relative p120ctn, p0071 is essential for cell division. Both, knock-down and overexpression of p0071 interfered with normal cell growth and survival due to cytokinesis defects with formation of multinucleated cells and induction of apoptosis. Cytokinesis depends on cytoskeletal reorganisation leading to contractile ring formation. Members of the Rho-family of GTPases are crucial regulators of this process. The failure of cytokinesis in response to altered p0071 expression correlated with the deregulation of Rho-activity. At the midbody, p0071 associated directly with active RhoA as well as with Ect2, the one Rho-guanine nucleotide exchange factor (GEF) essential in cytokinesis. P0071 stimulated RhoA-exchange activity in conjunction with Ect2. Although our findings support an essential role of p0071 in regulating spatially restricted Rho signalling during cytokinesis, its precise function at the contractile ring as well as its function in Rho signalling in other cellular contexts remains elusive. Therefore, we plan to investigate the role of p0071 in the local control of Rho signalling (1) in contractile ring formation during cytokinesis (2) in epithelial cell polarity and epithelial-mesenchymal transition and (3) in neurite outgrowth, retraction and branching.