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Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion
Yi Tang1, Zhongyu Liu, Ling Zhao
1Department of Pathology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA.
The Journal of Biological Chemistry
|July 3, 2008
Summary
Smad7 enhances cell-cell adhesion by stabilizing beta-catenin, preventing its degradation. This action increases the beta-catenin-E-cadherin complex at the cell membrane, modulating adhesion rather than Wnt signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Signal Transduction
Background:
- Beta-catenin is crucial for both cell adhesion and the canonical Wnt signaling pathway.
- Wnt signaling stabilizes beta-catenin, promoting nuclear translocation for gene regulation.
Purpose of the Study:
- To investigate the role of Smad7 in regulating beta-catenin stability and cell-cell adhesion.
- To elucidate the molecular mechanisms by which Smad7 influences beta-catenin localization and function.
Main Methods:
- Investigated Smad7-Axin interactions.
- Assessed the impact of Smad7 on beta-catenin phosphorylation and degradation.
- Analyzed the formation and stability of beta-catenin-E-cadherin complexes at the plasma membrane.
Main Results:
- Smad7 promotes cell-cell adhesion by stabilizing beta-catenin.
- Smad7 interacts with Axin, dissociating GSK-3beta and inhibiting Smurf2 recruitment to beta-catenin.
- This protection prevents beta-catenin phosphorylation and degradation, increasing its association with E-cadherin at the plasma membrane.
Conclusions:
- Smad7 stabilizes beta-catenin, enhancing cell-cell adhesion through the E-cadherin complex.
- Smad7-mediated stabilization of beta-catenin diverts it from nuclear translocation, thereby modulating cell adhesion over Wnt target gene transcription.
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