Heterologous expression of polycystin-1 inhibits endoplasmic reticulum calcium leak in stably transfected MDCK cells

摘要

autosomal DOMINANT polycystic kidney disease (ADPKD) is caused by loss of functional polycystin-1 or polycystin-2 (pel or pc2) (8, 9, 27). In affected individuals, renal function is gradually lost as normal renal parenchyma is progressively replaced by numerous cysts. A great deal has been learned about the functions of the polycystins in the decade since the identification of the two genes, but the exact way that loss of functional protein leads to cyst formation remains uncertain. Much of the experimental data points to a role for the polycystins in regulation of cell calcium (33). Polycystin-2 is a nonselective cation channel (22) that conducts calcium across the plasma membrane in concert with pel (19) and serves as a calcium release mediator across the endoplasmic reticulum (ER) membrane (22). pel has been implicated in the regulation of the pc2 channel (19, 36), and, with pc2, in the cell calcium response to deflection of the apical cilium (29).