Acute hypertonicity alters aquaporin-2 trafficking and induces a MAPK-dependent accumulation at the plasma membrane of renal epithelial cells

被引：14

作者：

Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02114-2790, United States ^{[1
]}

不详 ^{[2
]}

机构：

[1] Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston

[2] Service de Néphrologie, Fondation Pour Recherches Médicales, CH-1211, Geneva 4

来源：

J. Biol. Chem. | 2008年 / 39卷 / 26643-26661期

关键词：

Calmodulin - Enzymes - Cytology - Molecular biology;

D O I：

10.1074/jbc.M801071200

中图分类号：

学科分类号：

摘要：

The unique phenotype of renal medullary cells allows them to survive and functionally adapt to changes of interstitial osmolality/ tonicity. We investigated the effects of acute hypertonic challenge on AQP2 (aquaporin-2) water channel trafficking. In the absence of vasopressin, hypertonicity alone induced rapid (<10 min) plasma membrane accumulation of AQP2 in rat kidney collecting duct principal cells in situ, and in several kidney epithelial lines. Confocal microscopy revealed that AQP2 also accumulated in the trans-Golgi network (TGN) following hypertonic challenge. AQP2 mutants that mimic the Ser256 -phosphorylated and -nonphosphorylated state accumulated at the cell surface and TGN, respectively. Hypertonicity did not induce a change in cytosolic cAMP concentration, but inhibition of either calmodulin or cAMP-dependent protein kinase A activity blunted the hypertonicity-induced increase of AQP2 cell surface expression. Hypertonicity increased p38, ERK1/2, and JNK MAPK activity. Inhibiting MAPK activity abolished hypertonicity-induced accumulation of AQP2 at the cell surface but did not affect either vasopressin-dependent AQP2 trafficking or hypertonicity-induced AQP2 accumulation in the TGN. Finally, increased AQP2 cell surface expression induced by hypertonicity largely resulted from a reduction in endocytosis but not from an increase in exocytosis. These data indicate that acute hypertonicity profoundly alters AQP2 trafficking and that hypertonicity-induced AQP2 accumulation at the cell surface depends on MAP kinase activity. This may have important implications on adaptational processes governing transcellular water flux and/or cell survival under extreme conditions of hypertonicity. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

引用

页码：26643 / 26661

页数：18

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