In an effort to understand the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD), a relatively common genetic condition, Charron et al. (page 111) have elucidated key details of the molecular and cellular changes in ADPKD cells. Though the genes mutated in the majority of ADPKD cases, PKD1 and PKD2, were known, the roles of the associated gene products and the mechanisms that lead to the characteristic defects in cyst-lining epithelial cells have remained unclear.
Since polycystin-1, the product of the PKD1 gene, interacts with E-cadherin, the authors reasoned that mutations in PKD1 may affect cell morphology by disrupting E-cadherin assemblies. They found that ADPKD cells lack detectable E-cadherin on the cell surface, and that E-cadherin in the disease cells is sequestered in an intracellular pool. Though protein transport to the apical surface of ADPKD cells remained intact, trafficking...
