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

J Biol Chem. 2008 Sep 26;283(39):26643-61. doi: 10.1074/jbc.M801071200. Epub 2008 Jul 29.

Abstract

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 Ser(256)-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / drug effects
  • Adaptation, Physiological / physiology
  • Animals
  • Antidiuretic Agents / pharmacology
  • Aquaporin 2 / genetics
  • Aquaporin 2 / metabolism*
  • Biological Transport, Active / drug effects
  • Biological Transport, Active / physiology
  • Cell Line
  • Cyclic AMP / genetics
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytosol / metabolism
  • Endocytosis / drug effects
  • Endocytosis / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Golgi Apparatus / metabolism*
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mutation
  • Osmotic Pressure / drug effects
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Rats
  • Rats, Brattleboro
  • Vasopressins / pharmacology
  • Water / metabolism*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antidiuretic Agents
  • Aqp2 protein, rat
  • Aquaporin 2
  • Water
  • Vasopressins
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases