An inhibitory role of Rho in the vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells.
Vasopressin regulates water reabsorption in renal collecting duct principal cells by a cAMP-dependent translocation of the water channel aquaporin-2 (AQP2) from intracellular vesicles into the cell membrane. In the present work primary cultured inner medullary collecting duct cells were used to study the role of the proteins of the Rho family in the translocation of AQP2. Clostridium difficile toxin B, which inhibits all members of the Rho family, Clostridium limosum C3 toxin, which inactivates only Rho, and the Rho kinase inhibitor, Y-27632, induced both depolymerization of actin stress fibers and AQP2 translocation in the absence of vasopressin. The data suggest an inhibitory role of Rho in this process, whereby constitutive membrane localization is prevented in resting cells. Expression of constitutively active RhoA induced formation of actin stress fibers and abolished AQP2 translocation in response to elevation of intracellular cAMP, confirming the inhibitory role of Rho. Cytochalasin D induced both depolymerization of the F-actin cytoskeleton and AQP2 translocation, indicating that depolymerization of F-actin is sufficient to induce AQP2 translocation. Thus Rho is likely to control the intracellular localization of AQP2 via regulation of the F-actin cytoskeleton.
Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin-Buch, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
E
E
Klussmann
G
G
Tamma
D
D
Lorenz
B
B
Wiesner
K
K
Maric
F
F
Hofmann
K
K
Aktories
G
G
Valenti
W
W
Rosenthal
D000577:Amides / Q000494:pharmacology; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism*; D021381:Protein Transport; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D014667:Vasopressins / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
D000577:Amides; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D011725:Pyridines; D014667:Vasopressins; C108830:Y 27632; D000242:Cyclic AMP; D020741:rho GTP-Binding Proteins