Rho inhibits cAMP-induced translocation of aquaporin-2 into the apical membrane of renal cells

Am J Physiol Renal Physiol. 2001 Dec;281(6):F1092-101. doi: 10.1152/ajprenal.0091.2001.

Abstract

First published August 8, 2001; 10.1152/ajprenal.00091.2001.-We have recently demonstrated that actin depolymerization is a prerequisite for cAMP-dependent translocation of the water channel aquaporin-2 (AQP2) into the apical membrane in AQP2-transfected renal CD8 cells (29). The Rho family of small GTPases, including Cdc42, Rac, and Rho, regulates the actin cytoskeleton. In AQP2-transfected CD8 cells, inhibition of Rho GTPases with Clostridium difficile toxin B or with C. limosum C3 fusion toxin, as well as incubation with the Rho kinase inhibitor, Y-27632, caused actin depolymerization and translocation of AQP2 in the absence of the cAMP-elevating agent forskolin. Both forskolin and C3 fusion toxin-induced AQP2 translocation were associated with a similar increase in the osmotic water permeability coefficient. Expression of constitutively active RhoA induced formation of stress fibers and abolished AQP2 translocation in response to forskolin. Cytochalasin D induced both depolymerization of F-actin and AQP2 translocation, suggesting that depolymerization of F-actin is sufficient to induce AQP2 translocation. Together, these data indicate that Rho inhibits cAMP-dependent translocation of AQP2 into the apical membrane of renal principal cells by controlling the organization of the actin cytoskeleton.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amides / pharmacology
  • Animals
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins / metabolism*
  • Bacterial Toxins / pharmacology
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Polarity
  • Colforsin / pharmacology
  • Cyclic AMP / physiology*
  • Cytochalasin D / pharmacology
  • Cytoskeleton / drug effects
  • Cytoskeleton / ultrastructure
  • Enzyme Inhibitors / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Kidney Tubules, Collecting / metabolism*
  • Kidney Tubules, Collecting / ultrastructure
  • Protein Transport / drug effects
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Pyridines / pharmacology
  • Rabbits
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / physiology*
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein / physiology

Substances

  • Actins
  • Amides
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • Bacterial Toxins
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Pyridines
  • Y 27632
  • Colforsin
  • Cytochalasin D
  • Cyclic AMP
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein