The roles of catenins in the cadherin-mediated cell adhesion: Functional analysis of E-cadherin-α catenin fusion molecules

The carboxyl terminus-truncated cadherin (nonfunctional cadherin) has no cell adhesion activity probably because of its failure to associate with cytoplasmic proteins called α and β catenin. To rescue this nonfunctional cadherin as adhesion molecules, we constructed three cDNAs for fusion proteins between nonfunctional E-cadherin and α catenin, nEα, nEαN, and nEαC, where the intact, amino-terminal and carboxy-terminal half of α catenin, respectively, were directly linked to the nonfunctional E-cadherin, and introduced them into mouse L cells. The subcellular distribution and cell adhesion activity of nEα and nEαC molecules was similar to those of intact E-cadherin transfectants: they bound to cytoskeletons, were concentrated at cell-cell adhesion sites and showed strong cell adhesion activity. nEαN molecules, which also bound to cytoskeletons, showed very poor cell adhesion activity. Taken together, we conclude that in the formation of the cadherin- catenin complex, the mechanical association of α catenin, especially its carboxy-terminal half, with E-cadherin is a key step for the cadherin- mediated cell adhesion. Close comparison revealed that the behavior of nEα molecules during cytokinesis was quite different from that of intact E- cadherin, and that the intercellular motility, i.e., the cell movement in a confluent sheet, was significantly suppressed in nEα transfectants although it was facilitated in E-cadherin transfectants. Considering that nEα was not associated with endogenous β catenin in transfectants, the difference in the nature of cell adhesion between nEα and intact E-cadherin transfectants may be explained by the function of β catenin. The possible functions of β catenin are discussed with a special reference to its role as a negative regulator for the cadherin-mediated cell adhesion system.