A core function for p120-catenin in cadherin turnover

By Michael A. Davis, R. Ireton, Albert B. Reynolds. Journal of Cell Biology, 2003

788 citations recorded by the source corpus.

p120-catenin stabilizes epithelial cadherin (E-cadherin) in SW48 cells, but the mechanism has not been established. Here, we show that p120 acts at the cell surface to control cadherin turnover, thereby regulating cadherin levels. p120 knockdown by siRNA expression resulted in dose-dependent elimination of epithelial, placental, neuronal, and vascular endothelial cadherins, and complete loss of cell–cell adhesion. ARVCF and δ-catenin were functionally redundant, suggesting that proper cadherin-dependent adhesion requires the presence of at least one p120 family member. The data reveal a core function of p120 in cadherin complexes, and strongly predict a dose-dependent loss of E-cadherin in tumors that partially or completely down-regulate p120.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/891d9498b8f314db99853538bb4fe54423d52d38

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In Molecular Biology

1. Mahmut Yilmaz
2. C. Gottardi
3. T. Harris
4. U. Tepass
5. Gerhard Christofori
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7. M. Frame
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Citations in the corpus

• Phospho-regulation of β-Catenin Adhesion and Signaling Functions (2007, background): “p120ctn belongs to a subfamily of armadillo proteins and regulates cadherin surface levels by antagonizing endocytosis (17,83) and promoting cadherin clustering (87), possibly through its ability to inhibit Rho (79).”
• Regulation of cadherin-mediated adhesion in morphogenesis (2005, background): “Recently, p120 binding to cadherins has been found to regulate cadherin stability; loss of p120 expression leads to significantly reduced levels of E-cadherin in epitheli”
• Cadherin switching (2008, background): “Furthermore, Reynolds and co-workers and Kowalczyk and coworkers have independently shown that knocking down expression of p120-catenin by small interfering RNA (siRNA) results in decreased cadherin protein levels (Davis et al., 2003; Xiao et al., 2003).”
• E-cadherin–integrin crosstalk in cancer invasion and metastasis (2013, background): “By contrast, p120-catenin is reported to stabilise E-cadherin at the plasma membrane (Ireton et al., 2002) by controlling its cell surface levels through the regulation of cadherin trafficking (D’Souza-Schorey, 2005; Davis et al., 2003).”
• EMT, the cytoskeleton, and cancer cell invasion (2009, background): “The juxtamembrane domain of E-cadherin binds to p120-catenin which is important in surface tracking, lysosomal degradation and correct membrane localization of Ecadherin [27–30].”
• Adherens junctions: from molecules to morphogenesis (2010, background): “As discussed below, the cadherin–p120 catenin interaction counteracts cadherin endocytosis and degradation, and thus enhances the surface abundance of cadheri”
• Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. (2006, neutral): “2000), while stabilizing cadherins at the cell surface (Davis et al. 2003).”