( portance of cilia in the PKD pathology ...)Prestigious Wilson Award Goes To Yale Cell Biologist Joel Rosenbaum,Health

portance of cilia in the PKD pathology by demonstrating that the polycystins, gene products of the PKD genes, were located on these cilia. Because cilia were related directly to the disease, this became known as the “ciliary hypothesis of PKD.”

“Researchers at the NIH and Yale Medical School have now shown that these cilia bend when urine flows down the tubules, admitting calcium through the polycystins, which are mechano-receptors in the ciliary membrane. Through a signaling pathway, the calcium represses cell division,” said Rosenbaum. “If calcium does not flow in, because the cilia are missing, or the polycystins on the membrane are missing or ineffective, a signal is sent to the nucleus and the tubule cells divide—and continue to divide. PKD is, therefore, a cancer of the kidney, where cells that should not be dividing start to divide because of a defect in a signaling pathway starting at the cilium”

This sensory role of primary non-motile cilia has now become the model for many other diseases and syndromes, all of which trace back in many different tissues to defects in receptors or channels on the ciliary membrane, or to the complete lack of the cilium due to a defect in the IFT process.

Rosenbaum’s laboratory is now working on the connection between cilia and the cell cycle. “These primary non-motile cilia must resorb prior to cell division or the cell will not divide,” he said. Their latest work shows that when the amount of one of the IFT polypeptides, a small G protein, is decreased, the cell cycle is severely inhibited. This IFT small G-protein is a direct link between cilia and the cell cycle. In a normal cell cycle, the protein decreases, taking all the other IFT polypeptides with it, causing the cilia to shorten, and permitting the ciliary basal bodies/centrioles to migrate to the center of the cell to form the mitotic apparatus. Following chromosome separation, the amount of this IFT protein again increases, and the ce
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