Rho Inhibits cAMP-Induced Translocation of Aquaporin-2 into the Apical Membrane of Renal Cells

Title: Rho Inhibits cAMP-Induced Translocation of Aquaporin-2 into the Apical Membrane of Renal Cells
Authors: Tamma, Grazia; Klussmann, Enno; Maric, Kenan; Aktories, Klaus; Svelto, Maria; Rosenthal, Walter; Valenti, Giovanna
Publisher: American Journal of Physiology: Renal Physiology
Date Published: December 01, 2001
Reference Number: 554
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.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
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Aquaporin-2 (AQP2) is a protein which channels water through the cell membrane of the principal cells of the kidney collecting duct. To perform this function, it must move from a position in the cell interior to the cell membrane. A complex cascade of molecular events must occur to enable AQP2 to make this move to the cell membrane. Tamma, et al., investigated as to whether proteins of the Rho family are involved in AQP2s' movement to the cell membrane.

The researchers introduced agents that inhibited the function of Rho proteins into laboratory cell cultures rich in AQP2s. They found that when Rho or the Rho kinases were inhibited in the cell cultures, the cultures showed an increase in their ability to pass water. This indicated that the AQP2s were inserted in the cell membranes in the culture. This experiment indicates that Rho inhibits the movement of AQP2 to the cell membrane.

The researchers knew that the protein actin helps prevent the movement of cell particles from the interior of the cell to its membrane. And they knew that proteins of the Rho family help regulate the assembly of actin stress fibers. Their experiment showed that when Rho was inhibited, it caused actin to disassemble, which allowed the AQP2 to travel to the cell membrane.