Cystin, Cilia, and Cysts

Abstract

The past 10 yr has seen an exponential increase in research into a previously often ignored organelle, the primary cilium. This is largely as a result of the discovery that ciliary dysfunction underlies many human inheritable disorders, termed ciliopathies.1 These include polycystic kidney disease (PKD), nephronophthisis, and retinal degeneration. Cilia are microtubule-based organelles whose core components, the intraflagella transport proteins, are highly conserved evolutionarily from single-celled Chlamydomonas through to higher vertebrates, including humans.2 They are found on many different cell types, and their function varies greatly depending on the cell type from which they emanate. In renal epithelia, primary cilia protrude from the apical surface into the lumen of the nephron. Here, they are involved in the detection of fluid flow along the nephron. This is thought to occur by flow-induced bending of the cilium, which triggers calcium transients, an effect mediated through the polycystin 1/2 channel complex, both of the components of which are mutated in autosomal dominant PKD.3,4 Through the use of comparative genomics and proteomics, much has been learned about the gamut of proteins necessary for cilia formation and function; however, although it is well …