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Function of the armadillo protein p0071 in Rho signalling

犰狳蛋白 p0071 在 Rho 信号传导中的功能

基本信息

批准号：
40813496
负责人：
Professorin Dr. Mechthild Hatzfeld
金额：
--
依托单位：
Arbeitsgruppe Pathobiochemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2007
资助国家：
德国
起止时间：
2006-12-31 至 2010-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/40813496?language=en
关键词：
Function armadillo protein p0071 Rho

项目摘要

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.

我们最近发现了一个令人惊讶的新功能的犰狳蛋白p0071。与相对的p120 ctn不同，p0071是细胞分裂所必需的。p0071的敲低和过表达都干扰了正常细胞的生长和存活，这是由于胞质分裂缺陷，形成多核细胞和诱导凋亡。胞质分裂依赖于导致收缩环形成的细胞骨架重组。GTP酶的Rho家族成员是这一过程的关键调节剂。胞质分裂的失败与Rho活性的失调有关。在中体，p0071直接与活性RhoA以及与Ect 2相关，Ect 2是胞质分裂中必不可少的Rho-鸟嘌呤核苷酸交换因子（GEF）。P0071刺激RhoA交换活性与Ect 2结合。虽然我们的研究结果支持p0071在胞质分裂过程中调节空间限制的Rho信号传导中的重要作用，但其在收缩环的精确功能以及其在其他细胞环境中Rho信号传导中的功能仍然难以捉摸。因此，我们计划研究p0071在Rho信号传导的局部控制中的作用：（1）胞质分裂期间收缩环的形成;（2）上皮细胞极性和上皮-间充质转化;（3）神经突生长、收缩和分支。