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

Xiao Peng; Laura E Cuff; Cort D Lawton; Kris A DeMali

doi:10.1242/jcs.056432

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

Journal article

Open access

Peer reviewed

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

Xiao Peng, Laura E Cuff, Cort D Lawton and Kris A DeMali

Journal of cell science, Vol.123(Pt 4), pp.567-577

02/15/2010

DOI: 10.1242/jcs.056432

PMCID: PMC2818194

PMID: 20086044

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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.

Cell Line

Avian Proteins - metabolism

Mutagenesis, Site-Directed

Cadherins - metabolism

Humans

Vinculin - metabolism

Cell Membrane - physiology

Recombinant Fusion Proteins - metabolism

beta Catenin - metabolism

Adherens Junctions - metabolism

beta Catenin - genetics

Animals

Vinculin - genetics

RNA Interference

Cell Adhesion - physiology

Chickens

Protein Binding

Recombinant Fusion Proteins - genetics

Female

Vinculin - antagonists & inhibitors

Avian Proteins - genetics

Details

Title: Subtitle: Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin
Creators: Xiao Peng - Department of Biochemistry, University of Iowa Roy J. Carver College of Medicine, Iowa City, IA 52242, USA
Laura E Cuff
Cort D Lawton
Kris A DeMali
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.123(Pt 4), pp.567-577
DOI: 10.1242/jcs.056432
PMID: 20086044
PMCID: PMC2818194
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: England
Grant note: K01 CA111818 / NCI NIH HHS 1K01CA111818 / NCI NIH HHS
Language: English
Date published: 02/15/2010
Academic Unit: Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984024561202771

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