Hyperosmotic stimuli activate polycystin proteins to aid in urine concentration.

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. These proteins are thought to form a signaling complex that can flux cations, including calcium. One of the earliest symptoms in ADPKD is a decline in the concentrating ability of the kidneys, occurring prior to cyst formation. We reasoned that hyperosmolality stimulates the polycystin complex, and that the loss of this function impairs water reabsorption. We found that hyperosmolality resulted in the phosphorylation of microtubule-associated protein 4 (MAP4) in a PC1-dependent manner, which then elicited ER-localized PC2 calcium signals. ER-localized PC2 hyperosmotic calcium signals were required for trafficking of the water cha

SUBMITTER: Marquez-Nogueras KM 

PROVIDER: S-EPMC12487848 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature