The Role of Intercalated Cell Nedd4-2 in BP Regulation, Ion Transport, and Transporter Expression.

Détails

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Etat: Public
Version: Author's accepted manuscript
Licence: Non spécifiée
ID Serval
serval:BIB_A3FC0F6C0BF9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The Role of Intercalated Cell Nedd4-2 in BP Regulation, Ion Transport, and Transporter Expression.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Nanami M., Pham T.D., Kim Y.H., Yang B., Sutliff R.L., Staub O., Klein J.D., Lopez-Cayuqueo K.I., Chambrey R., Park A.Y., Wang X., Pech V., Verlander J.W., Wall S.M.
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
06/2018
Peer-reviewed
Oui
Volume
29
Numéro
6
Pages
1706-1719
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
BackgroundNedd4-2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between Nedd4-2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4-2 gene ablation on IC transporter abundance and function and on BP.Methods We generated IC Nedd4-2 knockout mice using Cre-lox technology and produced global pendrin/Nedd4-2 null mice by breeding global Nedd4-2 null (Nedd4-2 <sup>-/-</sup> ) mice with global pendrin null (Slc26a4 <sup>-/-</sup> ) mice. Mice ate a diet with 1%-4% NaCl; BP was measured by tail cuff and radiotelemetry. We measured transepithelial transport of Cl <sup>-</sup> and total CO <sub>2</sub> and transepithelial voltage in cortical collecting ducts perfused in vitro Transporter abundance was detected with immunoblots, immunohistochemistry, and immunogold cytochemistry.Results IC Nedd4-2 gene ablation markedly increased electroneutral Cl <sup>-</sup> /HCO <sub>3</sub> <sup>-</sup> exchange in the cortical collecting duct, although benzamil-, thiazide-, and bafilomycin-sensitive ion flux changed very little. IC Nedd4-2 gene ablation did not increase the abundance of type B IC transporters, such as AE4 (Slc4a9), H <sup>+</sup> -ATPase, barttin, or the Na <sup>+</sup> -dependent Cl <sup>-</sup> /HCO <sub>3</sub> <sup>-</sup> exchanger (Slc4a8). However, IC Nedd4-2 gene ablation increased CIC-5 total protein abundance, apical plasma membrane pendrin abundance, and the ratio of pendrin expression on the apical membrane to the cytoplasm. IC Nedd4-2 gene ablation increased BP by approximately 10 mm Hg. Moreover, pendrin gene ablation eliminated the increase in BP observed in global Nedd4-2 knockout mice.Conclusions IC Nedd4-2 regulates Cl <sup>-</sup> /HCO <sub>3</sub> <sup>-</sup> exchange in ICs., Nedd4-2 gene ablation increases BP in part through its action in these cells.
Mots-clé
Amiloride/analogs & derivatives, Amiloride/pharmacology, Animals, Bicarbonates/metabolism, Blood Pressure/genetics, Cell Membrane/metabolism, Chloride Channels/metabolism, Chloride-Bicarbonate Antiporters/metabolism, Chlorides/metabolism, Epithelial Sodium Channels/metabolism, Ion Exchange, Ion Transport/genetics, Kidney Tubules, Collecting/metabolism, Membrane Proteins/metabolism, Mice, Mice, Knockout, Nedd4 Ubiquitin Protein Ligases/genetics, Nedd4 Ubiquitin Protein Ligases/metabolism, Proton-Translocating ATPases/metabolism, Protons, Renal Reabsorption/drug effects, Sodium-Bicarbonate Symporters/metabolism, Sulfate Transporters/genetics, Sulfate Transporters/metabolism, Thiazides/pharmacology, chloride, cortical collecting duct, hypertension, intercalated cells, pendrin
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/05/2018 17:24
Dernière modification de la notice
18/09/2019 5:10
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