The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation.

Détails

ID Serval
serval:BIB_E51AF0676878
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation.
Périodique
Scientific reports
Auteur(s)
Rosenbaek L.L., Rizzo F., Wu Q., Rojas-Vega L., Gamba G., MacAulay N., Staub O., Fenton R.A.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
11/10/2017
Peer-reviewed
Oui
Volume
7
Numéro
1
Pages
12981
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
The renal sodium chloride cotransporter, NCC, in the distal convoluted tubule is important for maintaining body Na(+) and K(+) homeostasis. Endogenous NCC is highly ubiquitylated, but the role of individual ubiquitylation sites is not established. Here, we assessed the role of 10 ubiquitylation sites for NCC function. Transient transfections of HEK293 cells with human wildtype (WT) NCC or various K to R mutants identified greater membrane abundance for K706R, K828R and K909R mutants. Relative to WT-NCC, stable tetracycline inducible MDCKI cell lines expressing K706R, K828R and K909R mutants had significantly higher total and phosphorylated NCC levels at the apical plasma membrane under basal conditions. Low chloride stimulation increased membrane abundance of all mutants to similar or greater levels than WT-NCC. Under basal conditions K828R and K909R mutants had less ubiquitylated NCC in the plasma membrane, and all mutants displayed reduced NCC ubiquitylation following low chloride stimulation. Thiazide-sensitive sodium-22 uptakes were elevated in the mutants and internalization from the plasma membrane was significantly less than WT-NCC. K909R had increased half-life, whereas chloroquine or MG132 treatment indicated that K706 and K909 play roles in lysosomal and proteasomal NCC degradation, respectively. In conclusion, site-specific ubiquitylation of NCC plays alternative roles for NCC function.

Pubmed
Web of science
Open Access
Oui
Création de la notice
30/10/2017 17:25
Dernière modification de la notice
20/08/2019 16:08
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