Beyond regulation of cell adhesion -: Local control of RhoA at the cleavage furrow by the p0071 catenin
Beyond regulation of cell adhesion -: Local control of RhoA at the cleavage furrow by the p0071 catenin
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DOI：
10.4161/cc.6.2.3741
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发表时间：
2007-01-15
期刊：
影响因子：
4.3
通讯作者：
Hatzfeld, Mechthild
中科院分区：
文献类型：
--
作者：
Keil, Rene;Wolf, Annika;Hatzfeld, Mechthild
P120(ctn) 是犰狳蛋白亚家族的原型，该亚家族还包括 p0071、δ-连环蛋白、ARVCF 和关系较远的 plakophilins 1-3。这些蛋白质在调节粘附连接和桥粒形成方面具有明确的作用，这主要取决于它们聚集钙粘蛋白的能力。除了由膜相关池介导的细胞粘附功能外，这些蛋白质还显示出细胞质和细胞核定位。虽然它们的核功能仍然是个谜，但在了解它们的细胞质作用方面已经取得了重大进展。在细胞质中，p120 连环蛋白似乎负责各种细胞环境中小型 Rho-GTP 酶的时空控制。虽然 p120(ctn) 通过控制 Rho-GTP 酶在调节细胞粘附和运动方面具有主要功能，但最近的一份报告表明，密切相关的蛋白质 p0071 在胞质分裂过程中在卵裂沟处关联并调节 RhoA。 p0071 的过度表达和敲低会诱导胞质分裂缺陷，该缺陷是由收缩环 RhoA 活性上调或下调介导的。在那里，p0071 直接与 RhoA 本身以及 Rho-GEF Ect2 相互作用。 RhoA 的完全激活需要 Ect2 和 p0071，表明这两种蛋白在胞质分裂过程中协同作用来调节 RhoA。在这里，我们讨论 p120 连环蛋白作为多功能支架的功能，赋予 Rho-GTP 酶复杂调节特异性。通过在正确的时间和地点形成多蛋白复合物来控制大量刺激性鸟嘌呤交换因子 (GEF) 和抑制 GTP 酶激活蛋白 (GAP)，它们指导 Rho 信号传导的时空控制。
P120(ctn) is the prototype of a subfamily of armadillo proteins that also comprises p0071, delta-catenin, ARVCF and the more distantly related plakophilins 1-3. These proteins have well established roles in regulating adherens junction and desmosome formation which critically depends on their capacity to cluster cadherins. Besides this function in cell adhesion that is mediated by a membrane associated pool, these proteins also show cytoplasmic and nuclear localization. While their nuclear function is still enigmatic, major progress in understanding their cytoplasmic role has been made. In the cytoplasm, the p120 catenins appear responsible for the spatio-temporal control of small Rho-GTPases in various cellular contexts. Whereas p120(ctn) has a major function in regulating cell adhesion and motility through controlling Rho-GTPases, a recent report shows that the closely related protein p0071 associates and regulates RhoA at the cleavage furrow during cytokinesis. Overexpression and knockdown of p0071 induced a cytokinesis defect that was mediated by up- or downregulation of RhoA activity at the contractile ring. There, p0071 interacted directly with RhoA itself and with the Rho-GEF Ect2. Full activation of RhoA required Ect2 as well as p0071 indicating that these two proteins act in conjunction to regulate RhoA during cytokinesis. Here we discuss the function of p120 catenins as versatile scaffolds that confer specificity to the complex regulation of Rho-GTPases. By controlling numerous stimulating guanine exchange factors (GEFs) and inhibiting GTPase activating proteins (GAPs) via the formation of multiprotein complexes at the right time and place, they direct the spatio-temporal control of Rho-signalling.