Disease-associated missense mutations in the pore loop of polycystin-2 alter its ion channel function in a heterologous expression system.

ABSTRACT: Polycystin-2 (PC2) is mutated in ∼15% of patients with autosomal dominant polycystic kidney disease (ADPKD). PC2 belongs to the family of transient receptor potential (TRP) channels and can function as a homotetramer. We investigated whether three disease-associated mutations (F629S, C632R, or R638C) localized in the channel's pore loop alter ion channel properties of human PC2 expressed in Xenopus laevis oocytes. Expression of wild-type (WT) PC2 typically resulted in small but measurable Na⁺ inward currents in the absence of extracellular divalent cations. These currents were no longer observed when individual pore mutations were introduced in WT PC2. Similarly, Na⁺ inward currents mediated by the F604P gain-of-function (GOF) PC2 construct (PC2 F604P) were abolished

SUBMITTER: Staudner T 

PROVIDER: S-EPMC11630642 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature