Potassium depletion stimulates Na-Cl cotransporter via phosphorylation and inactivation of the ubiquitin ligase Kelch-like 3.

ABSTRACT: Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K⁺ secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K⁺ intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low-K⁺-mediated activation of Na-Cl cotransporter (NCC) in the kidney. In the distal convoluted tubules of mice eating a low-K⁺ diet, we found increased KLHL3 phosphorylation at S433 (KLHL3^S433-P), a modification that impairs WNK bind

SUBMITTER: Ishizawa K 

PROVIDER: S-EPMC5144580 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature