Ciliary function of polycystins: a new model for cystogenesis.

Abstract

Autosomal dominant polycystic kidney disease results from loss-of-function mutations in either polycystin-1 (Pc-1) or polycystin-2 (Pc-2). These transmembrane proteins directly interact through cytosolic domains of their C-termini. Pc-1 has been implicated in cell– extracellular matrix (ECM) interactions at focal adhesion contacts, but also in cell–cell interactions at tight junctions, adherens junctions and desmosomes [1]. Pc-2, located to the plasma membrane and/or to the endoplasmic reticulum [2,3], was shown to increase the intracytosolic calcium from both ER stocks and extracellular milieu [4]. The variability of polycystin localization within the cell may be explained by differences in antibody characteristics, cell type, degree of confluence, developmental stage, but also raises the hypothesis of multiple biological functions [1]. The large extracellular domain of Pc-1 is thought to transduce signals from the environment into the cells, through Pc-1-dependent signalling pathways and through activation of PC-2 calcium channel properties. However, the search for polycystin ligands and functions at sites of cell–cell or cell–ECM interactions has remained elusive to date. In fact, the first recently reported biological function of polycystins depends on an additional and unexpected polycystin subcellular localization—the renal primary cilia—and is triggered by an unexpected ligand, the urinary flow.