title: Rho inhibits cAMP-induced translocation of aquaporin-2 into the apical membrane of renal cells.
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.
authors.affiliation: Università di Bari, Dipartimento di Fisiologia Generale e Ambientale, 70126 Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tamma
authors.forename: E
authors.initials: E
authors.lastname: Klussmann
authors.forename: K
authors.initials: K
authors.lastname: Maric
authors.forename: K
authors.initials: K
authors.lastname: Aktories
authors.forename: M
authors.initials: M
authors.lastname: Svelto
authors.forename: W
authors.initials: W
authors.lastname: Rosenthal
authors.forename: G
authors.initials: G
authors.lastname: Valenti
mesh_terms: D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D000199:Actins; D000577:Amides; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D005576:Colforsin; D015638:Cytochalasin D; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein