Calcium-dependent Cell-Cell Adhesion Molecules (Cadherins): Subclass Specificities and Possible Involvement of Actin Bundles

Cadherins are a family of cell-cell adhesion molecules and are divided into subclasses with distinct adhesive specificities and tissue distribution. Here we examined the distribution of cadherins at contact sites between cells expressing the same or different cadherin subclasses. Each cadherin was concentrated at the boundary between cells expressing an identical cadherin subclass, irrespective of the cell types connected. However, such localization decreased or disappeared at the boundary between cells containing different cadherin subclasses. We also found that the localization of cadherins precisely coincided with that of actin bundles; both were detected at the apical region of cell sheets. This co-localization was retained even after cells were either treated with cytochalasin D or extracted with the detergent NP40. These results suggest that each cadherin subclass preferentially interacts with its own molecular type at intercellular boundaries, and that cadherin molecules may be associated with actinbased cytoskeletal elements. C ADHERINS are a family of glycoproteins which play a role in the Ca2§ cell-cell adhesion mechanism. They appear to have a major role in establishing and maintaining stable intercellular adhesion in most kinds of tissues (Takeichi et al., 1986). Cadherins are divided into subclasses, such as E-, N-, and P-types. In spite of their similar biochemical properties, different cadherins have distinct tissue distribution and distinct immunological and cell-binding specificities (Hatta et al., 1985; Hatta and Ihkeichi, 1986; Shirayoshi et al., 1986; Nose and Takeichi, 1986; Hatta et al., 1987). Our experiments have shown that cells with E-type do not adhere to cells with Nor P-type when they were mixed under the condition that only cadherins are active in linking cells (Takeichi et al., 1981, 1985; Nose and Takeichi, 1986). These results suggest that the specificity of each cadherin subclass plays an important role in preferential adhesion of cells with their own type. Several laboratories have identified cadherin-like molecules independently, such as uvomorulin (Peyrieras et al., 1983), L-CAM (Gallin et al., 1983), cell-CAM 120/80 (Damsky et al., 1983), Arc-1 (Behrens et al., 1985), and A-CAM (Volk and Geiger 1986a, b). It is believed that the first four molecules are identical to E-cadherin although animal species used for their identification are not all the same. We have actually found that the partial amino acid sequence of L-CAM reported by Cunningham et al. (1984) is identical to that of cadherins (Shirayoshi et al., 1986). A-CAM is similar to N-cadherin in its tissue distribution and biochemical properties, as discussed by Volk and Geiger (1986b). The molecular and structural basis of cadherin-dependent cell adhesion is unknown. Do cadherins bind cells in a homophilic or heterophilic manner? Are cadherins controlled by cytoskeletal elements? Why do cells with different cadherin subclasses segregate? Studies on uvomorulin (Boiler et al., 1985) showed that this molecule is concentrated in the adherens junction (the intermediate junction) in the intestinal epithelium. Volk and Geiger (1986a, b) showed that A-CAM is localized in the adherens-type junctions of heart and lens cells. Immunocytochemical studies of cadherins have also shown that they tend to be concentrated in the apical region of many epithelial tissues, where the intercellular adherens junctions are located (Hatta and Takeichi, 1986; Nose and Takeichi, 1986; Hatta et al., 1987). These observations suggest that cadherins are associated with specialized junctions such as the zonula adherens. In the present study, we have examined the distribution of cadherins on cells which are in contact with homologous or heterologous cells. We have also examined whether cadherins are associated with actin bundles. The results suggest that each subclass of cadherins interacts preferentially with its own type, and they appear to be associated with actin bundles. Materials and Methods