Structure-function relationships of the extracellular domain of the autosomal dominant polycystic kidney disease-associated protein, polycystin-1.

Polycystin-1 (PC-1) is a member of a novel family of proteins that have a multidomain structure. Although the C-terminal intracellular segments have been extensively studied, mainly with respect to their putative involvement in cell signalling, the potential function of the extracellular domains has received less attention. Mutations in PC-1 result in autosomal dominant polycystic kidney disease (ADPKD) which is characterised by perturbation of transport resulting in fluid accumulation, cell proliferation and modification of the extracellular matrix. The possibility that the interaction of a component of the extracellular matrix or some external factor with PC-1 may be important in the initiation or progression of ADPKD cannot currently be ruled out. The purpose of this review is to assess current evidence for the function of the PC-1 extracellular domains, and their potential implications for ADPKD.