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J Cell Sci. 2010 Feb 15;123(Pt 4):567-77. doi: 10.1242/jcs.056432. Epub 2010 Jan 19.

Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin.

Author information

1
Department of Biochemistry, University of Iowa Roy J. Carver College of Medicine, Iowa City, IA 52242, USA.

Abstract

Vinculin was identified as a component of adherens junctions 30 years ago, yet its function there remains elusive. Deletion studies are consistent with the idea that vinculin is important for the organization of cell-cell junctions. However, this approach removes vinculin from both cell-matrix and cell-cell adhesions, making it impossible to distinguish its contribution at each site. To define the role of vinculin in cell-cell junctions, we established a powerful short hairpin-RNA-based knockdown/substitution model system that perturbs vinculin preferentially at sites of cell-cell adhesion. When this system was applied to epithelial cells, cell morphology was altered, and cadherin-dependent adhesion was reduced. These defects resulted from impaired E-cadherin cell-surface expression. We have investigated the mechanism for the effects of vinculin and found that the reduced surface E-cadherin expression could be rescued by introduction of vinculin, but not of a vinculin A50I substitution mutant that is defective for beta-catenin binding. These findings suggest that an interaction between beta-catenin and vinculin is crucial for stabilizing E-cadherin at the cell surface. This was confirmed by analyzing a beta-catenin mutant that fails to bind vinculin. Thus, our study identifies vinculin as a novel regulator of E-cadherin function and provides important new insight into the dynamic regulation of adherens junctions.

PMID:
20086044
PMCID:
PMC2818194
DOI:
10.1242/jcs.056432
[Indexed for MEDLINE]
Free PMC Article

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