Identification and Localization of Polycystin, the PKD1 Gene Product

Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene ( PKD1 ) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within nor- mal tissues and the effects of ADPKD mutations on the pat- tern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an z 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistolog- ical studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron mi- croscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abun- dant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys. ( J. Clin. Invest. 1996. 98:2674-2682.) Key words: antibodiessubcellular localizationkidney development • cystic diseaseelectron microscope