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Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA. byoder@uab.edu
Cysts in the kidney are among the most common inherited human pathologies, and recent research has uncovered that a defect in cilia-mediated signaling activity is a key factor that leads to cyst formation. The cilium is a microtubule-based organelle that is found on most cells in the mammalian body. Multiple proteins whose functions are disrupted in cystic diseases have now been localized to the cilium or at the basal body at the base of the cilium. Current data indicate that the cilium can function as a mechanosensor to detect fluid flow through the lumen of renal tubules. Flow-mediated deflection of the cilia axoneme induces an increase in intracellular calcium and alters gene expression. Alternatively, a recent finding has revealed that the intraflagellar transport 88/polaris protein, which is required for cilia assembly, has an additional role in regulating cell-cycle progression independent of its function in ciliogenesis. Further research directed at understanding the relationship between the cilium, cell-cycle, and cilia-mediated mechanosensation and signaling activity will hopefully provide important insights into the mechanisms of renal cyst pathogenesis and lead to better approaches for therapeutic intervention.
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