Fig. 1.

Putative mechanism of calcium leak from ER in PKD. In PKD, a high level of intracellular cAMP activates PKA which in turn phosphorylates and enhances the gating activity of polycystin-2 (PC2), RyRs and IP3R in the ER. Constitutive activation of PC2, RyRs and IP3R results in calcium leak and depletion of the intracellular calcium store in PKD. Moreover, PC2 behaves as a brake to inhibit RyR activity, and dysfunction of PC2 may also cause calcium leak through RyRs. Polycystin-1 (PC1) inhibits PC2 activity through PP1-mediated dephosphorylation of PC2. PP1 interacts with PC1, and dysfunction of PC1 releases PP1-mediated PC2 dephosphorylation, thus promoting calcium leak through PC2.