The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area

Recent evidence suggests that structural and functional abnormalities of primary cilia in kidney epithelia are associated with mouse and human autosomal dominant polycystic kidney disease. To determine whether fibrocystin/polyductin/tigmin (FPC), the protein product encoded by the PKHD1 gene that is responsible for autosomal recessive polycystic kidney disease among human subjects, is also a component of primary cilia in the kidney, antipeptide antibodies to the carboxyl-terminal intracellular domain and amino-terminal extracellular domain of FPC were generated and were characterized with immunoblotting and immuno-light and -electron microscopy. Immunolocalization in normal kidney tissue sections and cultured kidney cells demonstrated that FPC was localized to the primary cilia and concentrated on the basal bodies in both kidney tissue sections and cultured kidney cells. The FPC expression pattern was not altered in kidney cells with Pkd1 mutations. These findings suggest that FPC is a functional and/or structural component of primary cilia in kidney tubular cells. It is proposed that the pathogenesis of autosomal recessive polycystic kidney disease is linked to the dysfunction of primary cilia.