Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients

• DOI: 10.1093/function/zqae031
• Publication Date: 2024-06-14T13:39:18Z
• Authors: Ana M Hernández-Vega; Itzel Llorente; Raúl Sánchez-Hern...; Yayoi Segura; Teresa Tusié-Luna; Luis E Morales-Bu...; Refugio García-Vi...; León D Islas; Tamara Rosenbaum
• Keywords: TRPV4; Identification

Abstract Polycystic kidney disease (PKD), a characterized by the enlargement of through cystic growth is fourth leading cause end-stage world-wide. Transient receptor potential Vanilloid 4 (TRPV4), calcium-permeable TRP, channel participates in cell physiology and since TRPV4 forms complexes with another whose malfunction associated to PKD, TRPP2 (or PKD2), we sought determine whether patients exhibit previously unknown mutations TRPV4. Here, report presence gene diagnosed PKD that they produce gain-of-function (GOF). Mutations sequence have been broad spectrum neuropathies skeletal dysplasias but not their biophysical effects on function elucidated. We identified examined functional behavior novel E6K mutant known S94L A217S TRVP4 channels. The mutation has mixed neuropathy and/or dysplasia phenotypes, however, carriers these variants had reported clinical manifestations. certain may influence progression severity GOF mechanisms. carrying are putatively more likely require dialysis or renal transplant as compared those without mutations.