Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells.
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.
Le Moellic
Cathy
C
INSERM U478, Faculté de Médecine Xavier Bichat, BP 416, 75870 Paris Cedex 18, France.
Boulkroun
Sheerazed
S
González-Nunez
Daniel
D
Dublineau
Isabelle
I
Cluzeaud
Francoise
F
Fay
Michel
M
Blot-Chabaud
Marcel
M
Farman
Nicolette
N
D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001693:Biological Transport, Active; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D062506:Claudin-4; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D007454:Iodides / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology*; D008353:Mannitol / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D062793:Occludin; D010617:Phenanthridines / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D012964:Sodium / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*
D000470:Alkaloids; D053119:Benzophenanthridines; D062506:Claudin-4; D007454:Iodides; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010617:Phenanthridines; D008353:Mannitol; D000450:Aldosterone; D012964:Sodium; C016299:chelerythrine; D011493:Protein Kinase C