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Am J Physiol Cell Physiol 289: C1513-C1521, 2005. First published August 17, 2005; doi:10.1152/ajpcell.00314.2005
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells

Cathy Le Moellic,1 Sheerazed Boulkroun,1 Daniel González-Nunez,1 Isabelle Dublineau,2 Francoise Cluzeaud,1 Michel Fay,1 Marcel Blot-Chabaud,1,* and Nicolette Farman1,*

1Institut National de la Santé et de la Recherche Médicale Unité 478, Institut Fédératif de Recherches 02, Faculté de Médecine Xavier Bichat, Paris; and 2Laboratoire de Radiobiologie Digestive, Institut de Protection et de Sûreté Nucléaire, Fontenay aux Roses, France

Submitted 29 June 2005 ; accepted in final form 10 August 2005

Aldosterone classically modulates Na transport in tight epithelia such as the renal collecting duct (CD) through the transcellular route, but it is not known whether the hormone could also affect paracellular permeability. Such permeability is controlled by tight junctions (TJ) that form a size- and charge-selective barrier. Among TJ proteins, claudin-4 has been highlighted as a key element to control paracellular charge selectivity. In RCCD2 CD cells grown on filters, we have identified novel early aldosterone effects on TJ. Endogenous claudin-4 abundance and cellular localization were unaltered by aldosterone. However, the hormone promoted rapid (within 15–20 min) and transient phosphorylation of endogenous claudin-4 on threonine residues, without affecting tyrosine or serine; this event was fully developed at 10 nM aldosterone and appeared specific for aldosterone (because it is not observed after dexamethasone treatment and it depends on mineralocorticoid receptor occupancy). Within the same delay, aldosterone also promoted an increased apical-to-basal passage of 125I (a substitute for 36Cl), whereas 22Na passage was unaffected; paracellular permeability to [3H]mannitol was also reduced. Later on (45 min), a fall in transepithelial resistance was observed. These data indicate that aldosterone modulates TJ properties in renal epithelial cells.

paracellular permeability; mannitol flux; occludin; iodine; sodium; kidney; RCCD2 cells


Address for reprint requests and other correspondence: N. Farman, INSERM U478, Faculté de Médecine Xavier Bichat, BP 416, 75870 Paris Cedex 18, France (e-mail: farman{at}bichat.inserm.fr)




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