This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tamma, G. Articles by Valenti, G. Search for Related Content PubMed PubMed Citation Articles by Tamma, G. Articles by Valenti, G.

Hypotonicity Induces Aquaporin-2 Internalization and Cytosol-to-Membrane Translocation of ICln in Renal Cells

Department of General and Environmental Physiology (G.T., G.P., A.S., M.S., G.V.), University of Bari, 70126 Bari, Italy; Department of Biomolecular Science and Biotechnology (E.B., G.M., M.P.), University of Milan, 20122 Milan, Italy; Department of Physiology and Medical Physics (G.T., M.P.), Medical University of Innsbruck, A-6020 Innsbruck, Austria; and Department of Physics and Laboratorio Regionale LICRYL (Liquid Crystal Laboratory) (V.F.), Istituto Nazionale Fisica della Materia-Consiglio Nazionale della Ricerca (INFM-CNR), University of Calabria, 87036 Calabria, Italy

Address all correspondence and requests for reprints to: Giovanna Valenti, Ph.D., Department of General and Environmental Physiology, University of Bari, Via Amendola 165/A, 70126 Bari, Italy; or Markus Paulmichl, Department of Biomolecular Sciences and Biotechnology, University of Milan, Via Celoria 26, 20133 Milano, Italy. E-mail: g.valenti{at}biologia.uniba.it; markus.paulmichl{at}i-med.ac.at; or markus.paulmichl{at}unimi.it.

Kidney collecting-duct cells swell in response to changes in medulla osmolality caused by the transition from antidiuresis to diuresis. Regulatory volume decrease (RVD) mechanisms must be activated to face this hypotonic stress. In Aquaporin-2 (AQP2)-expressing renal CD8 cells, hypotonicity decreased cell surface expression of AQP2 and increased the amount of AQP2 localized intracellularly, whereas the total amount of AQP2 phosphorylated at ser-256 decreased. Analysis of cAMP dynamics using fluorescence resonance energy transfer (FRET) showed that hypotonicity causes a reduction of cAMP, consistent with a decrease in phospho-AQP2. Moreover, hypotonicity caused a profound actin reorganization, associated with the loss of stress fibers and formation of F-actin patches (microspikes) at the cell border. Those changes were regulated by the monomeric GTPase Cdc42. Interestingly, expression of the dominant-negative Cdc42 (N17-Cdc42) prevented the hypotonicity-induced microspike formation and the generation of Cl^– currents. Hypotonicity also caused the relocation from the cytosol to the plasma membrane and increase in interaction with actin of ICln (nucleotide-sensitive chloride current protein), which is essential for the generation of ion currents activated during RVD. Together, the profound actin remodeling, internalization of AQP2 and translocation of ICln to the plasma membrane during hypotonicity may contribute to RVD after cell swelling in renal medulla.

This article has been cited by other articles:

				U. Hasler Controlled aquaporin-2 expression in the hypertonic environment Am J Physiol Cell Physiol, April 1, 2009; 296(4): C641 - C653. [Abstract] [Full Text] [PDF]

				G. Procino, C. Barbieri, G. Tamma, L. De Benedictis, J. E. Pessin, M. Svelto, and G. Valenti AQP2 exocytosis in the renal collecting duct - involvement of SNARE isoforms and the regulatory role of Munc18b J. Cell Sci., June 15, 2008; 121(12): 2097 - 2106. [Abstract] [Full Text] [PDF]