Ezrin-radixin-moesin–binding phosphoprotein 50 is expressed at the apical membrane of rat liver epithelia

Fouassier, Laura; Duan, Chengying; Feranchak, Andrew P.; Yun, Chris; Sutherland, Earl W.; Simon, Francis R.; Fitz, John; Doctor, R. Brian

doi:10.1053/jhep.2001.21143

Cited by 101 publications

(92 citation statements)

References 51 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously showed that EBP50 controls the activity of CFTR in cholangiocytes, presumably via the formation of a multiprotein complex with ezrin/protein kinase A. 5 In agreement with this model, the three binding partners CFTR, EBP50, and ezrin, had the same apical localization in human cholangiocytes. The complete overlap of CFTR with EBP50 in the luminal aspects of the cells ( Figure 1E, right) further supports the assumption that CFTR interacts with EBP50 at this site.…”

Section: Discussionsupporting

confidence: 66%

“…Whereas EBP50 was also detected in human hepatocytes, ezrin was not, in agreement with previous studies showing that radixin is the dominant ERM protein in hepatocytes. 5,27 It was recently shown that radixin is essential for maintaining the canalicular membrane structure and function in hepatocytes by interacting with canalicular transporters, in particular with multidrug-resistance-associated protein 2 (MRP2). 27,28 Although radixin is able to associate directly with the carboxy-terminal domain of MRP2 in vitro, there is evidence to indicate that MRP2 also binds radixin indirectly through a PDZ-containing protein, 28 and that EBP50 may act as the cross-linker between radixin and MRP2 29 or other transporters in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The liver is the tissue that displays the highest level of EBP50 expression. 3,4 We previously showed that in rat liver, EBP50 is expressed both in hepatocytes and in cholangiocytes, and that, in the latter, the interaction of cystic fibrosis transmembrane conductance regulator (CFTR) with the PDZ1 domain of EBP50 is required for cAMP-dependent chloride secretion, 5 suggesting an important role of EBP50 in bile secretory functions.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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

show abstract

Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…Abnormal expression of scaffold proteins has been linked to different types of cancer in human (Claperon and Therrien, 2007). Ezrin-radixinmoesin-(ERM)-binding phosphoprotein 50 (EBP50; also named NHERF-1 for Na þ /H þ exchanger regulatory factor-1) is a scaffold protein that is strongly expressed in the liver, and in particular beneath the plasma membrane of biliary epithelial cells (Fouassier et al, 2001(Fouassier et al, , 2009. Previous studies have suggested that EBP50 could also form protein complexes at the adherens junctions (AJs), by directly interacting with b-catenin (Shibata et al, 2003;Kreimann et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

et al. 2011

Self Cite

View full text Add to dashboard Cite

Scaffold proteins form multiprotein complexes that are central to the regulation of intracellular signaling. The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is highly expressed at the plasma membrane of normal biliary epithelial cells and binds epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with oncogenic properties. This study investigated EBP50-EGFR interplay in biliary cancer. We report that in a collection of 106 cholangiocarcinomas, EBP50 was delocalized to the cytoplasm of tumor cells in 66% of the cases. Ectopic expression of EBP50 was correlated with the presence of satellite nodules and with the expression of EGFR, which was at the plasma membrane, implying a loss of interaction with EBP50 in these cases. In vitro, loss of interaction between EBP50 and EGFR was mimicked by EBP50 depletion using a small interfering RNA approach in human biliary carcinoma cells co-expressing the two proteins at their plasma membrane, and in which interaction between EBP50 and EGFR was validated. EBP50 depletion caused an increase in EGFR expression at their surface, and a sustained activation of the receptor and of its downstream effectors (extracellular signal-regulated kinase 1/2, signal transducer and activator of transcription 3) in both basal and EGF-stimulated conditions. Cells lacking EBP50 showed epithelial-to-mesenchymal transition-associated features, including reduction in E-cadherin and cytokeratin-19 expression, induction of S100A4 and of the E-cadherin transcriptional repressor, Slug, and loss of cell polarity. Accordingly, depletion of EBP50 induced the disruption of adherens junctional complexes, the development of lamellipodia structures and the subsequent acquisition of motility properties. All these phenotypic changes were prevented upon inhibition of EGFR tyrosine kinase by gefitinib. These findings indicate that loss of EBP50 at the plasma membrane in tumor cells may contribute to biliary carcinogenesis through EGFR activation.

show abstract

“…The ERM (Ezrin, Radixin and Moesin) family of proteins plays an important role in regulating the structure and function of specific domains of the cell cortex by crosslinking membrane and actin cytoskeleton 4 . The dominant ERM protein in hepatocytes is radixin 5 , which is primarily localized at the canalicular membrane of hepatocytes 5,6 . At four weeks of age radixin-knock out mice demonstrate a selective loss of Mrp2 from the canalicular membrane and begin to develop conjugated hyperbilirubinemia, reminiscent of the DubinJohnson syndrome in man 7 .…”

Section: Introductionmentioning

confidence: 99%

Radixin Is Required to Maintain Apical Canalicular Membrane Structure and Function in Rat Hepatocytes

et al. 2006

View full text Add to dashboard Cite

show abstract

Ezrin-radixin-moesin–binding phosphoprotein 50 is expressed at the apical membrane of rat liver epithelia

Abstract: Ezrin-radixin-moesin (ERM)-

Cited by 101 publications

References 51 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

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

Radixin Is Required to Maintain Apical Canalicular Membrane Structure and Function in Rat Hepatocytes

Contact Info

Product

Resources

About