February 2002

From Journal of Clinical Investigation

Ciliary proteins and polycystic kidneys

Polycystin 1 and 2 mutations represent the most common cause of dominantly inherited polycystic kidney disease. However, humans and mice are also subject to recessive disorders in which the kidneys, and sometimes the liver, pancreas, or ovaries, are subject to cyst formation. In mice, the analysis of these mutations has led to interest in the role of apical cilia in the development of these tissues and in a seemingly unrelated matter, the genesis of a left-right axis during embryogenesis. Several ciliary proteins, including one of the dynein-class motor proteins and polaris, a protein found in the basal body and the ciliary axoneme, are affected by these mutations. Hou and colleagues have now found that the mouse cpk gene encodes another such ciliary protein, termed cystin, a putative scaffold protein that may bind directly to the axonemal membrane. Cystin, like polaris, localizes to the axoneme of kidney cell cilia and is presumed to have a similar distribution in biliary and other epithelial cells. Mutation of cpk leads to renal and biliary cysts but is not reported to disrupt left-right asymmetry in development. However, the body axis formation phenotype seen, for instance, in animals with defects in polaris appears to reflect a need for motile cilia, which direct a leftward flow of extracellular fluid across an embryonic structure called the ?node?. In contrast, the cilia in the kidney and elsewhere are frequently nonmotile and may play other roles, perhaps in mechanosensory signaling. Whatever these roles, cystin would be predicted to be particularly needed in these structures, but perhaps not in the nodal cilia. Whether a cystin homolog is a candidate for human autosomal recessive polycystic kidney disease is still unknown, since no such sequence is identifiable in the current draft of the human genome sequence.











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