Expression of polycystin-1 C-terminal fragment enhances the ATP-induced Ca super(2+) release in human kidney cells

Polycystin-1 (PC1) is a membrane protein expressed in tubular epithelia of developing kidneys and in other ductal structures. Recent studies indicate this protein to be putatively important in regulating intracellular Ca super(2+) levels in various cell types, but little evidence exists for kidney epithelial cells. Here we examined the role of the PC1 cytoplasmic tail on the activity of store operated Ca super(2+) channels in human kidney epithelial HEK-293 cell line. Cells were transiently transfected with chimeric proteins containing 1-226 or 26-226 aa of the PC1 cytoplasmic tail fused to the transmembrane domain of the human Trk-A receptor: TrkPC1 wild-type and control Trk truncated peptides were expressed at comparable levels and localized at the plasma membrane. Ca super(2+) measurements were performed in cells co-transfected with PC1 chimeras and the cytoplasmic Ca super(2+)-sensitive photoprotein aequorin, upon activation of the phosphoinositide pathway by ATP, that, via purinoceptors, is coupled to the release of Ca super(2+) from intracellular stores. The expression of TrkPC1 peptide, but not of its truncated form, enhanced the ATP-evoked cytosolic Ca super(2+) concentrations. When Ca super(2+) assays were performed in HeLa cells characterized by Ca super(2+) stores greater than those of HEK-293 cells, the histamine-evoked cytosolic Ca super(2+) increase was enhanced by TrkPC1 expression, even in absence of external Ca super(2+). These observations indicate that the C-terminal tail of PC1 in kidney and other epithelial cells upregulates a Ca super(2+) channel activity also involved in the release of intracellular stores.