Chasing the cilium: a deeper understanding of ciliary biology opens new doors on disorders from diabetes to schizophrenia.(Research)(Cover Story)

Most biologists are familiar with motile cilia, the fingerlike appendages that allow unicellular organisms to swim, and the specialized cells that move fluids and clear away debris in our kidneys and lungs. Few are aware, though, that nearly every cell in the human body also possesses a single immotile or "primary" cilium. The functions of primary cilia are quite obscure, and until recently they were considered to be vestigial.

Ciliary biology has undergone a quiet revolution. Defects in primary cilia are now proposed to contribute to such diverse disorders as diabetes, obesity, and schizophrenia. At the same time, ciliary biologists are gaining a better understanding of disorders caused by defects in motile cilia, such as chronic respiratory disease and abnormal organ development. "There is quite a broad range of human disorder that is going to be caused by ciliary dysfunction," predicts Nicholas Katsanis of Johns Hopkins University, who studies Bardet-Biedl syndrome, a genetic disorder of ciliary origin.

This revolution largely resulted from the groundbreaking discovery of intraflagellar transport, or IFT, the process by which cells form cilia and flagella. IFT's discovery led directly to the finding that defects in primary cilia of kidney cells cause a common genetic disorder, polycystic kidney disease (PKD), which sparked renewed interest in these once overlooked organelles.

Researchers are working to identify the estimated 300 to 500 proteins that make up all cilia, as well as those involved in IFT. New studies of PKD and other disorders are showing that defects in primary and motile cilia can have profound effects on cell division and human development. While the exact functions of primary cilia are still unknown, growing evidence suggests that these organelles act as cellular antennae, receiving chemical or mechanical signals critical to controlling growth, differentiation, and proliferation.

UNCONTROLLED CELL DIVISION In the roughly 1 in 1,000 people affected by PKD, multiple fluid-filled cysts develop in their kidneys due to uncontrolled cell proliferation. The end …