Na+/H+ Exchanger Regulatory Factor Isoform 1 Overexpression Modulates Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Expression and Activity in Human Airway 16HBE14o- Cells and Rescues ΔF508 CFTR Functional Expression in Cystic Fibrosis Cells*

Guerra, Lorenzo; Fanelli, Teresa; Favia, Maria; Riccardi, Stefania Maria; Busco, Giovanni; Cardone, Rosa Angela; Carrabino, Salvatore; Weinman, Edward J.; Reshkin, Stephan J.; Conese, Massimo; Casavola, Valeria

doi:10.1074/jbc.m505103200

Cited by 88 publications

(106 citation statements)

References 55 publications

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“…Whether EBP50 undergoes cytoplasmic delocalization in homozygous ⌬F508 CFTR bronchial epithelial cells is a matter of debate. 39, 40 Here we show that ⌬F508 CFTR mutation is neither sufficient nor necessary for EBP50 to undergo delocalization in cholangiocytes. Accordingly, delocalization of EBP50 was absent in the native bile ducts from ⌬F508 CF patients and present in the ductular cells from non CF patients.…”

Section: Discussionmentioning

confidence: 98%

Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation

Fouassier

Rosenberg

Mergey

et al. 2009

The American Journal of Pathology

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Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) anchors and regulates apical membrane proteins in epithelia. EBP50 is inducible by estrogen and may affect cell proliferation, although this latter function remains unclear. The goal of this study was to determine whether EBP50 was implicated in the ductular reaction that occurs in liver disease. EBP50 expression was examined in normal human liver, in human cholangiopathies (ie, cystic fibrosis, primary biliary cirrhosis, and primary sclerosing cholangitis), and in rats subjected to bile-duct ligation. The regulation of EBP50 by estrogens and its impact on proliferation were assessed in both bile duct-ligated rats and Mz-Cha-1 human biliary epithelial cells. Analyses of cell isolates and immunohistochemical studies showed that in normal human liver, EBP50 is expressed in the canalicular membranes of hepatocytes and, together with ezrin and cystic fibrosis transmembrane conductance regulator, in the apical domains of cholangiocytes. In both human cholangiopathies and bile duct-ligated rats, EBP50 was redistributed to the cytoplasmic and nuclear compartments. EBP50 underwent a transient increase in rat cholangiocytes after bile-duct ligation, whereas such expression was down-regulated in ovariectomized rats. In addition, in Mz-Cha-1 cells, EBP50 underwent upregulation and intracellular redistribution in response to 17␤-estradiol, whereas its proliferation was inhibited by siRNA-mediated EBP50 knockdown. These results indicate that both the expression and distribution of EBP50 are regulated by estrogens and contribute to the proliferative response in biliary epithelial cells. (Am J

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Section: Discussionmentioning

confidence: 98%

Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation

Fouassier

Rosenberg

Mergey

et al. 2009

The American Journal of Pathology

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“…Knockdown of EBP50 in immortalized airway epithelial cells has been reported to reduce the surface stability of both wtCFTR and low-temperature r⌬F508CFTR (24). In contrast, overexpression of EBP50 was found to rescue ⌬F508CFTR in CFBE41o-cells by a mechanism that involved cytoskeletal reorganization through EBP50-RhoA-Rho kinase-ezrin interactions (25,26).…”

mentioning

confidence: 80%

“…As such, data were summarized in bar graph format (Fig. 2D), showing median (blue) and inter-quartile (25 th to 75 th percentiles, red) range values. As described above, data from MDCK cell lines (Fig.…”

Section: Increased Cell Surface Diffusion Of R⌬f508cftrmentioning

confidence: 99%

Reduced PDZ Interactions of Rescued ΔF508CFTR Increases Its Cell Surface Mobility

Valentine

Lukacs

Haggie

2012

Journal of Biological Chemistry

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Background: Phenylalanine 508 deletion from CFTR (⌬F508CFTR) is the most common cause of CF. Results: Diffusional mobility of surface ⌬F508CFTR is greater than that of wild type CFTR, irrespective of ⌬F508CFTR rescue mechanism. Conclusion: Defective ⌬F508CFTR-PDZ interactions result in greater ⌬F508CFTR diffusion and could contribute to its enhanced internalization. Significance: Restoring ⌬F508CFTR-scaffold interaction may have therapeutic benefit.

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“…Accordingly, both inhibition of CAL protein expression and NHERF1 overexpression are efficient in promoting the cell surface expression and function of the most common diseaseassociated mutant, F508del-CFTR (Bossard et al, 2007;Guerra et al, 2005;Wolde et al, 2007). Interestingly, the conformational and molecular interactions between CFTR and CAL differ from those between CFTR and NHERF1, indicating that PDZ-selective inhibitors can be designed to improve CFTR mutant expression (Amacher et al, 2011;Cushing et al, 2010;Piserchio et al, 2005).…”

Section: Cal Targets Cftr To Lysosomal Degradationmentioning

confidence: 99%

Fine Tuning of CFTR Traffic and Function by PDZ Scaffolding Proteins

Bossard¹,

Silantieff²,

Gauthier³

2012

Cystic Fibrosis - Renewed Hopes Through Research

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Na+/H+ Exchanger Regulatory Factor Isoform 1 Overexpression Modulates Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Expression and Activity in Human Airway 16HBE14o- Cells and Rescues ΔF508 CFTR Functional Expression in Cystic Fibrosis Cells*

Cited by 88 publications

References 55 publications

Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation

Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation

Reduced PDZ Interactions of Rescued ΔF508CFTR Increases Its Cell Surface Mobility

Fine Tuning of CFTR Traffic and Function by PDZ Scaffolding Proteins

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