The Cadherin-11 Cytoplasmic Juxtamembrane Domain Promotes α-Catenin Turnover at Adherens Junctions and Intercellular Motility

Kiener, Hans P.; Stipp, Christopher S.; Allen, Philip G.; Higgins, Jonathan M.G.; Brenner, Michael B.

doi:10.1091/mbc.e05-08-0745

Cited by 34 publications

(27 citation statements)

References 46 publications

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“…The data are also consistent with a recent study suggesting that the p120-binding juxtamembrane domain of cadherin 11 is responsible for cadherin 11–mediated cell motility (Kiener et al, 2006). …”

Section: Discussionsupporting

confidence: 92%

p120 catenin is essential for mesenchymal cadherin–mediated regulation of cell motility and invasiveness

Yanagisawa

Anastasiadis

2006

The Journal of Cell Biology

120

166

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During epithelial tumor progression, the loss of E-cadherin expression and inappropriate expression of mesenchymal cadherins coincide with increased invasiveness. Reexpression experiments have established E-cadherin as an invasion suppressor. However, the mechanism by which E-cadherin suppresses invasiveness and the role of mesenchymal cadherins are poorly understood. We show that both p120 catenin and mesenchymal cadherins are required for the invasiveness of E-cadherin–deficient cells. p120 binding promotes the up-regulation of mesenchymal cadherins and the activation of Rac1, which are essential for cell migration and invasiveness. p120 also promotes invasiveness by inhibiting RhoA activity, independently of cadherin association. Furthermore, association of endogenous p120 with E-cadherin is required for E-cadherin–mediated suppression of invasiveness and is accompanied by a reduction in mesenchymal cadherin levels. The data indicate that p120 acts as a rheostat, promoting a sessile cellular phenotype when associated with E-cadherin or a motile phenotype when associated with mesenchymal cadherins.

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Section: Discussionsupporting

confidence: 92%

p120 catenin is essential for mesenchymal cadherin–mediated regulation of cell motility and invasiveness

Yanagisawa

Anastasiadis

2006

The Journal of Cell Biology

120

166

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“…The mean diffusion coefficients of VE-cad-GFP determined from 50 individual trajectories for each transfection condition were estimated to (5 Ϯ 1) ϫ 10 Ϫ2 m 2 ⅐s Ϫ1 for control-as well as for EPLIN siRNA-treated HUVECs. This value is consistent with data published on E-cad-GFP (24), GFP-N-cad (26), and cad-11-GFP (27) when involved in mature cell-cell contacts. The fact that VE-cad diffusion is not affected by EPLIN depletion suggests that the primary function of EPLIN is not to control VEcad-mediated stability at adherens junctions.…”

Section: Eplin Is Not Essential For Stability Of Mature Ve-cadherinmesupporting

confidence: 93%

Epithelial Protein Lost In Neoplasm (EPLIN) Interacts with α-Catenin and Actin Filaments in Endothelial Cells and Stabilizes Vascular Capillary Network in Vitro

Chervin-Pétinot

Courçon

Almagro

et al. 2012

Journal of Biological Chemistry

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Background: Cohesion of interendothelial junctions is maintained by the connections existing between the VE-cadherin⅐catenin complex and the actin cytoskeleton. Results: By interacting with ␣-catenin, the actin-binding protein EPLIN (epithelial protein lost in neoplasm) facilitates the recruitment of vinculin. Conclusion:The EPLIN␣-catenin link provides a mechanosensory machinery by acting as a tension transmitter. Significance: By anchoring the VE-cadherin⅐catenin complex to F-actin, EPLIN strengthens interendothelial junctions.

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“…65 Furthermore, certain domains of Cad-11 play specific functions in mediating cell polarity and cell-cell interactions, and targeting these specific domains may prove to be most effective. 66, 67 Future work investigating the benefits of these inhibitors for prevention or treatment of CAVD may help clinicians arrive at a therapeutic solution to the debilitating disease.…”

Section: Discussionmentioning

confidence: 99%

Cadherin-11 Overexpression Induces Extracellular Matrix Remodeling and Calcification in Mature Aortic Valves

Sung

Bowen

Vaidya

et al. 2016

ATVB

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Objective Calcific aortic valve disease is a significant clinical problem for which the regulatory mechanisms are poorly understood. Enhanced cell-cell adhesion is a common mechanism of cellular aggregation, but its role in calcific lesion formation is not known. Cadherin-11 (Cad-11) has been associated with lesion formation in vitro, but its function during adult valve homeostasis and pathogenesis is not known. This study aims to elucidate the specific functions of Cad-11 and its downstream targets RhoA and Sox9 in extracellular matrix remodeling and aortic valve calcification. Approach and Results We conditionally overexpressed Cad-11 in murine heart valves using a novel double transgenic Nfatc1Cre;R26-Cad11Tg/Tg mouse model. These mice developed hemodynamically significant aortic stenosis with prominent calcific lesions in the aortic valve leaflets. Cad-11 overexpression upregulated downstream targets RhoA and Sox9 in the valve interstitial cells, causing calcification and extensive pathogenic extracellular matrix remodeling. Aortic valve interstitial cells overexpressing Cad-11 in an osteogenic environment in vitro rapidly form calcific nodules analogous to in vivo lesions. Molecular analyses revealed upregulation of osteoblastic and myofibroblastic markers. Treatment with a ROCK inhibitor attenuated nodule formation, further supporting that Cad-11 driven calcification acts through the small GTPase RhoA/ROCK signaling pathway. Conclusions This study identifies one of the underlying molecular mechanisms of heart valve calcification and demonstrates that overexpression of Cad-11 upregulates RhoA and Sox9 to induce calcification and extracellular matrix remodeling in adult aortic valve pathogenesis. The findings provide a potential molecular target for clinical treatment.

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The Cadherin-11 Cytoplasmic Juxtamembrane Domain Promotes α-Catenin Turnover at Adherens Junctions and Intercellular Motility

Cited by 34 publications

References 46 publications

p120 catenin is essential for mesenchymal cadherin–mediated regulation of cell motility and invasiveness

p120 catenin is essential for mesenchymal cadherin–mediated regulation of cell motility and invasiveness

Epithelial Protein Lost In Neoplasm (EPLIN) Interacts with α-Catenin and Actin Filaments in Endothelial Cells and Stabilizes Vascular Capillary Network in Vitro

Cadherin-11 Overexpression Induces Extracellular Matrix Remodeling and Calcification in Mature Aortic Valves

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