A DROSOPHILA HOMOLOG OF CADHERIN ASSOCIATED WITH ARMADILLO AND ESSENTIAL FOR EMBRYONIC CELL-CELL ADHESION

We have identified a Drosophila homolog of vertebrate classic cadherin s. A monoclonal antibody to Drosophila alpha-catenin (D alpha-catenin) copurifies a 150-kDa glycoprotein (gp150) along with the alpha-cateni n. To further characterize this protein, we generated monoclonal antib odies to gp150 and isolated its cDNAs using the antibodies. Predicted sequences of the encoded product revealed that it is a transmembrane p rotein with similarity to vertebrate classic cadherins, and so we desi gnated this molecule DE-cadherin. The extracellular domain has six cad herin-specific repeats, although the first repeat seems to be cleaved off upon maturation, and the cytoplasmic domain shows significant iden tity to that of vertebrate classic cadherins. DE-cadherin is distingui shable from its vertebrate counterparts by a large insertion with loca l sequence similarity to Fat, laminin A chain, Slit, and neurexin I at the proximal region of the extracellular domain. Despite such differe nces, DE-cadherin is functionally similar to vertebrate classic cadher ins. For example, it is associated with alpha-catenin and beta-catenin (Armadillo), and protected from trypsin digestion only in the presenc e of Ca2+, as is the case for many of classic cadherins. Transfection of S2 cells with the DE-cadherin cDNA enhances their Ca2+-dependent ce ll aggregation. Antibodies to this molecule inhibited aggregation of n ot only the transfectants but also early embryonic cells. DE-cadherin is concentrated at the apical poles of epithelial cell-cell junctions. All these results suggest that DE-cadherin is a homolog of vertebrate classic cadherins and that the vertebrate and invertebrate share comm on mechanisms for regulation of cell-cell adhesion. (C) 1994 Academic Press, Inc.