IDENTIFICATION AND LOCALIZATION OF POLYCYSTIN, THE PKD1 GENE-PRODUCT

Polycystin, the product of autosomal dominant polycystic kidney diseas e (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of pro teins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collect ed in the current study: the subcellular localization of polycystin, t he spatial and temporal distribution of the protein within normal tiss ues and the effects of ADPKD mutations on the pattern of expression in affected tissues, Antisera directed against a synthetic peptide and t wo recombinant proteins of different domains of polycystin revealed th e presence of an similar to 400-kD protein (polycystin) in the membran e fractions of normal fetal, adult, and ADPKD kidneys. Immunohistologi cal studies localized polycystin to renal tubular epithelia. hepatic b ite ductules, and pancreatic ducts, all sites of cystic changes in ADP KD, as web as in tissues such as skin that are not known to be affecte d in ADPKD. By electron microscopy, polycystin was predominantly assoc iated with plasma membranes. Polycystin was significantly less abundan t in adult than in fetal epithelia. In contrast, polycystin was overex pressed in most, but not all, cysts in ADPKD kidneys.