Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Mol Biol Cell. 2011 Nov;22(22):4247-55. doi: 10.1091/mbc.E11-03-0250. Epub 2011 Sep 21.
Cadherin-catenin interactions play an important role in cadherin-mediated adhesion. Here we present strong evidence that in the cadherin-catenin complex α-catenin contributes to the binding strength of another catenin, p120, to the same complex. Specifically, we found that a β-catenin-uncoupled cadherin mutant interacts much more weakly with p120 than its full-size counterpart and that it is rapidly endocytosed from the surface of A-431 cells. We also showed that p120 overexpression stabilizes this mutant on the cell surface. Examination of the α-catenin-deficient MDA-MB-468 cells and their derivates in which α-catenin was reintroduced showed that α-catenin reinforces E-cadherin-p120 association. Finally, a cross-linking analysis of the cadherin-catenin complex indicated that a large loop located in the middle of the p120 arm-repeat domain is in close spatial vicinity to the amino-terminal VH1 domain of α-catenin. The six amino acid-long extension of this loop, caused by an alternative splicing, weakens p120 binding to cadherin. The data suggest that α-catenin-p120 contact within the cadherin-catenin complex can regulate cadherin trafficking.
钙黏蛋白-连环蛋白相互作用在钙黏蛋白介导的黏附中起重要作用。在这里，我们提供了强有力的证据表明，在钙黏蛋白-连环蛋白复合物中，α-连环蛋白有助于另一种连环蛋白 p120 与同一复合物的结合强度。具体来说，我们发现 β-连环蛋白分离的钙黏蛋白突变体与 p120 的相互作用比其全长对应物弱得多，并且它从 A-431 细胞表面迅速内吞。我们还表明，p120 的过表达稳定了该突变体在细胞表面的表达。对 MDA-MB-468 细胞及其衍生的 α-连环蛋白缺陷细胞的研究表明，α-连环蛋白增强了 E-钙黏蛋白-p120 的结合。最后，对钙黏蛋白-连环蛋白复合物的交联分析表明，位于 p120 臂重复结构域中间的一个大环与 α-连环蛋白的氨基末端 VH1 结构域在空间上非常接近。该环的六氨基酸长延伸是由选择性剪接引起的，削弱了 p120 与钙黏蛋白的结合。数据表明，钙黏蛋白-连环蛋白复合物中的 α-连环蛋白-p120 接触可以调节钙黏蛋白的运输。
