The lipid 5-phoshatase SHIP2 controls renal brush border ultrastructure and function by regulating the activation of ERM proteins
| Autor: | Stéphane Schurmans, François Jouret, Sufyan Ali Sayyed, David Perez-Morga, Marjorie Vermeersch |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Glucose Male Phosphatidylinositol 4 5-Diphosphate rho GTP-Binding Proteins Mice 129 Strain Time Factors Brush border Genotype Swine Moesin 030232 urology & nephrology Nephron Renal protein reabsorption Kidney Tubules Proximal 03 medical and health sciences 0302 clinical medicine Phosphatidylinositol Phosphates Radixin Glycosuria medicine Animals Mice Knockout Renal oligopeptide reabsorption Microvilli Reabsorption Chemistry Microfilament Proteins Fanconi syndrome Membrane Proteins Epithelial Cells medicine.disease Renal Reabsorption Cell biology Mice Inbred C57BL Cytoskeletal Proteins 030104 developmental biology medicine.anatomical_structure Phenotype Nephrology Multiprotein Complexes Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases LLC-PK1 Cells Female |
| Zdroj: | Kidney international. 92(1) |
| ISSN: | 1523-1755 |
| Popis: | The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knockout mice, proximal tubule–specific Ship2 knockout mice, and a proximal tubule cell model in which SHIP2 is inactivated, we show that SHIP2 is a negative regulator of microvilli formation, thereby controlling solute reabsorption by the proximal tubule. We found increased PtdIns(4,5)P2 substrate and decreased PtdIns4P product when SHIP2 was inactivated, associated with hyperactivated ezrin/radixin/moesin proteins and increased Rho-GTP. Thus, inactivation of SHIP2 leads to increased microvilli formation and solute reabsorption by the renal proximal tubule. This may represent an innovative therapeutic target for renal Fanconi syndrome characterized by decreased reabsorption of solutes by this nephron segment. |
| Databáze: | OpenAIRE |
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