Piezo1 dictates K⁺ homeostasis through coordinated regulation of the ubiquitin ligase Kelch-like 3 in RBCs and the kidney.

ABSTRACT: The maintenance of potassium (K⁺) balance is a fundamental biological process involving multiple tissues. However, the roles of intertissue crosstalk in K⁺ homeostasis remain poorly understood. Here, we demonstrate that the mechanosensor Piezo1 dictates extracellular K⁺ homeostasis by orchestrating the ubiquitin ligase Kelch-like 3 (KLHL3) activity in red blood cells (RBCs; erythrocytes) and the kidney. Genetic variants within KLHL3 with expression quantitative trait locus effects are associated with altered RBC parameters, and CRISPR-generated KLHL3 knock-in (KLHL3-KI) mice carrying a nonphosphorylatable Ala substitution at its activation site (Ser433) reveal that KLHL3 regulates erythrocyte volume by modulating with-no-lysine 1 (WNK1). In wild-type

SUBMITTER: Ishizawa K 

PROVIDER: S-EPMC12818455 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature