Cleavage of N-terminus of polycystin-1 increases calcium permeability of polycystin-1/2 receptor channel complexes.

ABSTRACT: Mutations on genes encoding polycystin-1 (PC1) and PC2 cause autosomal-dominant polycystic kidney disease. How these 2 proteins work together to exert anticystogenesis remains elusive. PC1 resembles adhesion G-protein coupled receptors and undergoes autocleavage in the extracellular N-terminus to expose a hidden "stalk" region, which is hypothesized to act as a "tethered agonist." Here, we show that WT PC1 and PC2 formed functional heteromeric channel complexes in Xenopus oocytes with different biophysical properties from PC2 homomeric channels. Deletion of PC1 N-terminus, which exposed the stalk, increased calcium permeability in PC1/PC2 heteromers that required the presence of stalk. Extracellular application of synthetic stalk peptide increased calcium permeation in stalkless PC1/PC2. A

SUBMITTER: Wang R 

PROVIDER: S-EPMC12513491 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature