Ciliary functions of cystoproteins: mechanosensation and cell cycle control. Polycystin-1 (PC-1), polycystin-2 (PC-2) and other cystoproteins (not shown) are expressed in primary cilia, basal bodies or centrosomes. The primary cilium forms in fully differentiated cells in the G0 phase of the cell cycle. A cilium protrudes from the basal body (centrosome) formed by two centrioles, a mother centriole (blue cylinder) and a daughter centriole (orange cylinder). As cells enter the cell cycle, the cilium is resorbed, and the centrosome can act as a mitotic spindle pole organizer. Flow-induced bending of cilia in renal epithelial cells triggers Ca2+ influx mediated by PC-2 in association with PC-1.The role of ciliary proteins in cell cycle control is supported by several findings: (1) In the normal state, PC-2 sequesters Id2 [proproliferative helix-loop-helix (HLH) protein] in the cytoplasm, preventing it from entering the nucleus. In PKD, when PC-1 or PC-2 are inactivated, Id2 translocates to the nucleus and interacts with E-protein, blocking its ability to induce growth-suppressive genes and resulting in increased activity of cdk2 and activation of cell proliferation; (2) PC-1 can activate the JAK/STAT signaling pathway, resulting in the induction of p21waf1 and cell cycle arrest in G0 and G1; (3) The intraflagellar transport component IFT88/polaris is capable of controlling G1/S transition of the cell cycle. IFT88/polaris remains associated with the centrosome throughout the cell cycle, where it forms a complex with Che-1, thus modulating its binding to Rb protein.
