Cellular and subcellular distribution of polycystin-2, the protein productof the PKD2 gene

Mutations in the PKD1 and PKD2 genes account for 85 and 15% of cases of aut osomal dominant polycystic kidney disease, respectively. Polycystin-2, the product of the PKD2 gene, is predicted to be an integral membrane protein w ith homology to a family of voltage-activated Ca2+ channels. In vitro studi es suggest that it may interact with polycystin-1, the PKD1 gene product, v ia coiled-coil domains present in their C-terminal domains. In this study, the cellular and subcellular distribution of polycystin-2 is defined and co mpared with polycystin-1. A panel of rabbit polyclonal antisera was raised against polycystin-2 and shown to recognize a single band consistent with p olycystin-2 in multiple tissues and cell lines by immunoprecipitation and W estern blotting. Immunostaining of human and murine renal tissues demonstra ted widespread and developmentally regulated expression of polycytin-2, wit h highest levels in the kidney in the thick ascending limbs of the loop of Henle and the distal convoluted tubule. In contrast, polycystin-1 expressio n, while localizing to the same tubular segments, was highest in the collec ting ducts. Immunohistochemical staining and immunofluorescence microscopy localized polycystin-2 to the basolateral plasma membrane of kidney tubular epithelial cells compared with the junctional localization of polycystin-1 . Differences in the developmental, cellular, and subcellular expression of polycystin-1 and polycystin-2 suggest that they may be able to function in dependently of each other in addition to a potential in vivo interaction vi a their C-termini.