alpha T-Catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion

Cadherins are major cell-cell adhesion proteins whose cytoplasmic domains b ind to catenin proteins. Strong intercellular adhesion depends on linkage o f the cadherin/catenin complex to the actin cytoskeleton via alpha -catenin . To date, it is not clear how different cell types achieve the variable st rength of cell-cell adhesion clearly needed in a multicellular organism. He re, we report the cloning and molecular characterization of alphaE(testis)c atenin, a novel human cDNA encoding a protein with homology to both human a lphaE(epithelial)-catenin and alphaN(neural)-catenin. Although originally d iscovered in testis, alphaT-catenin is expressed in other tissues, the high est levels being observed in heart. Immunohistochemical analysis showed hum an alphaT-catenin localization at intercalated discs of cardiomyocytes and in peritubular myoid cells of testis. In cells transfected with alphaT-cate nin cDNA, interaction with beta -catenin was demonstrated by coimmunoprecip itation. Transfection of alpha -catenin-deficient colon carcinoma cells rec ruited E-cadherin and beta -catenin to cell-cell contacts and functional ca dherin-mediated cell-cell adhesion was restored in this way. Moreover, comp action of these cells was at least as prominent as in the case of cells exp ressing endogenous alphaE-catenin. We propose that alphaT-catenin is necess ary for the formation of stretch-resistant cell-cell adhesion complexes, in particular, muscle cells.