Identification of the region of α-catenin that plays an essential role in cadherin-mediated cell adhesion

α-连环蛋白是钙粘附素黏附复合体的固有成分，是一个102kDa的蛋白质，具有多个相互作用部位，包括同源二聚部位、β-和γ-连环蛋白(斑点)、α-肌动蛋白和肌动蛋白的结合部位。然而，除了与β-或γ-连环蛋白的结合外，还不清楚哪些相互作用对钙粘连蛋白的功能至关重要。通过在白血病细胞(K562)上表达一系列E-钙粘蛋白-α-连环蛋白嵌合分子，我们已经确定了α-连环蛋白区域，该区域赋予无功能的无尾E-钙粘蛋白诱导聚集活性。该区域已被定位到α-连环蛋白的第295个氨基酸残基上。该区域含有F-肌动蛋白的结合部位。与此结果一致的是，在α-连环蛋白缺陷细胞(DLD-1/Δα)中，表达由上述实验中确定的氨基末端α-连环蛋白结合位点和羧基末端细胞粘附区组成的突变β-/γ-连环蛋白分子可诱导E-钙粘连蛋白介导的细胞聚集和致密。然而，表达E-钙粘素嵌合分子的细胞与包含纽蛋白肌动蛋白结合部位的纽蛋白的同源羧基末端区域不同，不像表达E-钙粘蛋白-α-连环蛋白嵌合分子的细胞那样聚集。

α-Catenin is an intrinsic component of the cadherin adhesion complex and is a 102 kDa protein with multiple interaction sites, including homodimerization sites, and binding sites for β- and γ-catenin (plakoglobin), α-actinin, and actin. Besides the binding to β- or γ-catenin, it is unknown, however, which interaction is critical for the function of cadherins. By expressing a series of E-cadherin-α-catenin chimeric molecules on leukemia cells (K562), we have identified the region of α-catenin that confers aggregation-inducing activity to nonfunctional tail-less E-cadherin. The region has been mapped to the carboxy-terminal 295 amino acids of α-catenin. The region contains a binding site for F-actin. Consistent with this result, expression in α-catenin deficient cells ( DLD-1/Δα) of a mutant α-catenin molecule consisting of the amino-terminal β-/γ-catenin-binding site and the carboxy-terminal cell adhesion region identified in the above experiments induced E-cadherin-mediated cell aggregation and compaction. Cells expressing E-cadherin chimeric molecules with the homologous carboxy-terminal region of vinculin, which contains the actin-binding site of vinculin, did not, however, aggregate as strongly as ones expressing E-cadherin-α-catenin chimeric molecules.