特集 生体膜を三重層としてとらえる カドヘリン・カテニン複合体

Abstract

E-cadherin (uvomorulin) is a member of the Ca2+-dependent cell adhesion molecules (cadherins). Its cytoplasmic region complexes with structurally distinct proteins termed α-, β-, and γ-catenins. cDNA cloning has revealed that α-catenin is a vinculin homologue whereas β-catenin is closely related to plakoglobin. A specific recognition site for catenins has been located in a carboxyl-terminal 72 amino acid domain (the catenin-binding domain). The association with catenins is of crucial importance for the cell adhesion function of E-cadherin, since mutant E-cadherins with deletions in the catenin-binding domain show no activity in cell aggregation assays. A cell line, which express E-cadherin and catenins except for α-catenin, shows poor adhesiveness but transfection of cDNA for αN-catenin, a subtype of α-catenin, results in an increased adhessiveness of the cells. A combination of biochemical analyses on the molecular organization of the E-cadherin-catenin complex has shown that a single complex is composed of one molecule of E-cadherin, one molecule of α-catenin, and one molecule of β-catenin. β-catenin has been shown to interact directly with E-cadherin. In pulse-chase experiments β-catenin is already associated with the 135 kD E-cadherin precursor molecule but the assembly of the newly synthesized α-, and γ-catenin into the complex is only detected around the time of endoproteolytic processing. Transformation of cells with v-src results in tyrosine phosphorylation of the cadherin-catenin complex and perturbed cadherin-mediated cell adhesion whereas a tyrosine kinase inhibitor revertes the effect of transformation. These results suggest a possible role of the tyrosine phosphorylation of the complex in regulating cadherin function.