The polycystic kidney disease 1 gene product modulates Wnt signaling

Two distinct signaling pathways, involving Wnt signaling and polycystin, ha ve been found to be critical for normal kidney development. Renal tubulogen esis requires the presence of certain Wnt proteins, whereas mutations in po lycystin impede the terminal differentiation of renal tubular epithelial ce lls, causing the development of large cystic kidneys that characterize auto somal dominant polycystic kidney disease. Polycystin is an integral membran e protein, consisting of several extracellular motifs indicative of cell-ce ll and cell-matrix interactions, coupled through multiple transmembrane dom ains to a functionally active cytoplasmic domain. We report here that expre ssion of the C-terminal cytoplasmic domain of polycystin stabilizes soluble endogenous beta-catenin and stimulates TCF-dependent gene transcription in human embryonic kidney cells. Microinjection of the polycystin C-terminal cytoplasmic do main induces dorsalization in zebrafish, Our findings sugges t that polycystin has the capacity to modulate Wnt signaling during renal d evelopment.