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-Catenin Results in
Stable Colocalization of Mutant -Catenin with
Adenomatous Polyposis Coli Protein and
Altered MDCK Cell Adhesion
* Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305-5426;
and Department of Anatomy, Department of Biochemistry and Cardiovascular Research Institute, University of California at
San Francisco, San Francisco, California 94143-0452
-Catenin is essential for the function of cadherins, a family of Ca2+-dependent cell-cell adhesion
molecules, by linking them to 
-catenin and the actin
cytoskeleton. -Catenin also binds to adenomatous polyposis coli (APC) protein, a cytosolic protein that is
the product of a tumor suppressor gene mutated in
colorectal adenomas. We have expressed mutant
-catenins in MDCK epithelial cells to gain insights
into the regulation of -catenin distribution between cadherin and APC protein complexes and the functions
of these complexes. Full-length -catenin, -catenin
mutant proteins with NH2-terminal deletions before
(
N90) or after (N131, N151) the -catenin binding
site, or a mutant -catenin with a COOH-terminal deletion (C) were expressed in MDCK cells under the
control of the tetracycline-repressible transactivator.
All -catenin mutant proteins form complexes and
colocalize with E-cadherin at cell-cell contacts; N90,
but neither N131 nor N151, bind -catenin. However, -catenin mutant proteins containing NH2-terminal deletions also colocalize prominently with APC
protein in clusters at the tips of plasma membrane protrusions; in contrast, full-length and COOH-terminal- deleted -catenin poorly colocalize with APC protein.
NH2-terminal deletions result in increased stability of
-catenin bound to APC protein and E-cadherin, compared with full-length -catenin. At low density,
MDCK cells expressing NH2-terminal-deleted -catenin mutants are dispersed, more fibroblastic in morphology, and less efficient in forming colonies than parental MDCK cells. These results show that the NH2
terminus, but not the COOH terminus of -catenin,
regulates the dynamics of -catenin binding to APC protein and E-cadherin. Changes in -catenin binding
to cadherin or APC protein, and the ensuing effects
on cell morphology and adhesion, are independent of
-catenin binding to -catenin. These results demonstrate that regulation of -catenin binding to E-cadherin and APC protein is important in controlling epithelial cell adhesion.
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