Evolutionary conservation of Drosophila polycystin-2 as a calcium-activated cation channel

Mutations in the PKD2 gene cause autosomal dominant polycystic kidney disease (ADPKD) in humans. The protein encoded by PKD2 has similarity to voltage-sensitive cation channels and TRP channels and was named polycystin-2 (PC2). In agreement with this structural information, expression of PC2 in Xenopus oocytes or reconstitution of human PC2 in planar lipid bilayers produced Ca(2+)-activated cation channels. Although these studies provided a basic description of the biophysical, regulatory, and pharmacologic properties of the PC2-induced channels, it is still unknown how defective PC2 activity leads to cyst formation and expansion in ADPKD patients. To establish a genetic model for studying PC2 function and regulation, the authors identified and cloned a Drosophila PC2 (DmPC2). It is here shown that expression of DmPKD2 in Drosophila S2 cells produced a novel channel. On the basis of the similarity of this channel's properties to mammalian PKD2-induced channels, this Drosophila channel is expected to provide a convenient genetic model for dissecting the mechanisms underlying ADPKD.