NH2-TERMINAL DELETION OF BETA-CATENIN RESULTS IN STABLE COLOCALIZATION OF MUTANT BETA-CATENIN WITH ADENOMATOUS POLYPOSIS-COLI PROTEIN AND ALTERED MDCK CELL-ADHESION

beta-Catenin is essential for the function of cadherins, a family of C a2+-dependent cell-cell adhesion molecules, by linking them to alpha-c atenin and the actin cytoskeleton, beta-Catenin also binds to adenomat ous polyposis coli (APC) protein, a cytosolic protein that is the prod uct of a tumor suppressor gene mutated in colorectal adenomas. We have expressed mutant beta-catenins in MDCK epithelial cells to gain insig hts into the regulation of beta-catenin distribution between cadherin and APC protein complexes and the functions of these complexes. Full-l ength beta-catenin, beta-catenin mutant proteins with NH2-terminal del etions before (Delta N90) or after (Delta N131,Delta N151) the alpha-c atenin binding site, or a mutant beta-catenin with a COOH-terminal del etion (Delta C) were expressed in MDCK cells under the control of the tetracycline-repressible transactivator. All beta-catenin mutant prote ins form complexes and colocalize with E-cadherin at cell-cell contact s; Delta N90, but neither Delta N131 nor Delta N151, bind alpha-cateni n. However, beta-catenin mutant proteins containing NH2-terminal delet ions also colocalize prominently with APC protein in clusters at the t ips of plasma membrane protrusions; in contrast, full-length and COOH- terminal-deleted beta-catenin poorly colocalize with APC protein. NH2- terminal deletions result in increased stability of beta-catenin bound to APC protein and E-cadherin, compared with full-length beta-catenin . At low density, MDCK cells expressing NH2-terminal-deleted beta-cate nin mutants are dispersed, more fibroblastic in morphology, and less e fficient in forming colonies than parental MDCK cells. These results s how that the NH2 terminus, but not the COOH terminus of beta-catenin, regulates the dynamics of beta-catenin binding to APC protein and E-ca dherin. Changes in beta-catenin binding to cadherin or APC protein, an d the ensuing effects on cell morphology and adhesion, are independent of beta-catenin binding to alpha-catenin. These results demonstrate t hat regulation of beta-catenin binding to E-cadherin and APC protein i s important in controlling epithelial cell adhesion.