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

ABSTRACT: 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

SUBMITTER: Rosenbaek LL 

PROVIDER: S-EPMC5636807 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature