SHIP2 regulates epithelial cell polarity through its lipid product, which binds to Dlg1, a pathway subverted by hepatitis C virus core protein
| Autor: | Ronan Barre, Clotilde Cariven, Aline Awad, Jean Pierre Salles, Christophe Erneux, Didier Samuel, Mickaël Marin, Sokhavuth Sar, Ama Gassama-Diagne |
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| Rok vydání: | 2013 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate RHOA Hepacivirus Viral Core Proteins -- genetics -- metabolism Discs Large Homolog 1 Protein chemistry.chemical_compound Phosphatidylinositol 3-Kinases Phosphatidylinositol Phosphates Adaptor Proteins Signal Transducing -- genetics -- metabolism Cell polarity Phosphatidylinositol 4 5-Diphosphate -- metabolism Protein Isoforms RNA Small Interfering Hepacivirus -- physiology Epithelial polarity Kinase Viral Core Proteins Cell Polarity Articles Sciences bio-médicales et agricoles Cell biology Phosphatidylinositol Phosphates -- metabolism Cell Biology of Disease Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases Host-Pathogen Interactions Epithelial Cells -- metabolism -- virology Hepatocytes -- metabolism -- virology RNA Small Interfering -- genetics -- metabolism Sciences exactes et naturelles Signal Transduction Polarity (physics) RAC1 Biology Sciences de l'ingénieur Cell Line Dogs Animals Humans Phosphatidylinositol Molecular Biology Adaptor Proteins Signal Transducing Phosphoric Monoester Hydrolases -- antagonists & inhibitors -- genetics -- metabolism Phosphatidylinositol 3-Kinases -- genetics -- metabolism Membrane Proteins Lipid metabolism Généralités Epithelial Cells Cell Biology Molecular biology Phosphoric Monoester Hydrolases chemistry Gene Expression Regulation Membrane Proteins -- genetics -- metabolism biology.protein Hepatocytes Protein Isoforms -- antagonists & inhibitors -- genetics -- metabolism |
| Zdroj: | Molecular Biology of the Cell Molecular biology of the cell, 24 (14 |
| ISSN: | 1939-4586 |
| Popis: | The main targets of hepatitis C virus (HCV) are hepatocytes, the highly polarized cells of the liver, and all the steps of its life cycle are tightly dependent on host lipid metabolism. The interplay between polarity and lipid metabolism in HCV infection has been poorly investigated. Signaling lipids, such as phosphoinositides (PIs), play a vital role in polarity, which depends on the distribution and expression of PI kinases and PI phosphatases. In this study, we report that HCV core protein, expressed in Huh7 and Madin-Darby canine kidney (MDCK) cells, disrupts apicobasal polarity. This is associated with decreased expression of the polarity protein Dlg1 and the PI phosphatase SHIP2, which converts phosphatidylinositol 3,4,5-trisphosphate into phosphatidylinositol 4,5-bisphosphate (PtdIns(3,4)P2). SHIP2 is mainly localized at the basolateral membrane of polarized MDCK cells. In addition, PtdIns(3,4)P2 is able to bind to Dlg1. SHIP2 small interfering RNA or its catalytically dead mutant disrupts apicobasal polarity, similar to HCV core. In core-expressing cells, RhoA activity is inhibited, whereas Rac1 is activated. Of interest, SHIP2 expression rescues polarity, RhoA activation, and restricted core level in MDCK cells. We conclude that SHIP2 is an important regulator of polarity, which is subverted by HCV in epithelial cells. It is suggested that SHIP2 could be a promising target for anti-HCV treatment. Journal Article Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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