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J. Biol. Chem., Vol. 276, Issue 23, 20451-20457, June 8, 2001
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From the 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.
An Inhibitory Role of Rho in the Vasopressin-mediated
Translocation of Aquaporin-2 into Cell Membranes of Renal Principal
Cells*
§,,,,
,,**
Forschungsinstitut für Molekulare
Pharmakologie, Campus Berlin-Buch, Robert-Rössle-Strasse 10, 13125 Berlin, Germany, the ¶ Universita de Bari, Dipartimento di
Fisiologia Generale e Ambientale, Via Amendola 165/A, 70126 Bari,
Italy, the Institut für Pharmakologie und Toxikologie,
Albert-Ludwigs-Universität Freiburg, Hermann Herder Strasse 5,
79104 Freiburg, and the ** Freie Universität Berlin, Institut
für Pharmakologie, Thielallee 67-73, 14195 Berlin, Germany
*
This work was supported by Deutsche Forschungsgemeinschaft
Grant Ro 597/6 and the Fond der Chemischen Industrie.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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