Function of the armadillo protein p0071 in Rho signalling

我们最近发现了犰狳蛋白p0071的一个令人惊讶的新功能。与相对的p120ctn不同，p0071对细胞分裂至关重要。p0071基因的敲除和过表达都干扰了正常的细胞生长和存活，导致细胞分裂缺陷，形成多核细胞，诱导细胞凋亡。细胞质分裂依赖于导致收缩环形成的细胞骨架重组。GTPases的rho家族成员是这一过程的关键调控者。p0071表达改变导致的细胞分裂失败与rho活性的解除相关。在中间，p0071与活跃的RhoA和Ect2直接相关，Ect2是细胞分裂中必不可少的一个RhoA鸟嘌呤核苷酸交换因子（GEF）。P0071与Ect2共同刺激rhoa交换活性。尽管我们的研究结果支持p0071在细胞分裂过程中调节空间限制性Rho信号传导的重要作用，但其在收缩环上的确切功能以及在其他细胞环境下的Rho信号传导功能仍然难以捉摸。因此，我们计划研究p0071在Rho信号的局部控制中的作用(1)在细胞分裂期间的收缩环形成(2)在上皮细胞极性和上皮-间质转化(3)在神经突的生长、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.