Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherinand the catenins

Autosomal dominant polycystic kidney disease (ADPKD) is a common human gene tic disease characterized by cyst formation in kidney tubules and other duc tular epithelia. Cells lining the cysts have abnormalities in cell prolifer ation and cell polarity. The majority of ADPKD cases are caused by mutation s in the PKD1 gene, which codes for polycystin-1, a large integral membrane protein of unknown function that is expressed on the plasma membrane of re nal tubular epithelial cells in fetal kidneys. Because signaling from cell- cell and cell-matrix adhesion complexes regulates cell proliferation and po larity, we speculated that polycystin-1 might interact with these complexes . We show here that polycystin-1 colocalized with the cell adhesion molecul es E-cadherin and alpha-, beta-, and gamma-catenin. Polycystin-1 coprecipit ated with these proteins and comigrated with them on sucrose density gradie nts, but it did not colocalize, coprecipitate, or comigrate with focal adhe sion kinase, a component of the focal adhesion. We conclude that polycystin -1 is in a complex containing E-cadherin and alpha-, beta-, and gamma-caten in. These observations raise the question of whether the defects in cell pr oliferation and cell polarity observed in ADPKD are mediated by E-cadherin or the catenins.