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Motoring Proteins and Genetic Disease

01.08.2005


A defect in the mechanics of motors that build tiny cellular hairs is the basis of a serious genetic disorder, according to researchers at UC Davis and Simon Fraser University, Canada. Bardet-Biedl syndrome (BBS), affecting about one in 100,000 births, includes progressive blindness, extra or fused fingers and toes, kidney disease and learning difficulties, among other problems.



Products of genes linked to the syndrome coordinate mobile, cargo-carrying motor proteins within the cilia, tiny hairs found on the surface of cells, according to graduate student Guangshuo Ou, postgraduate researcher Joshua Snow and Jonathan Scholey, professor of molecular and cellular biology at UC Davis, and postdoctoral researcher Oliver Blacque and Professor Michel Leroux at Simon Fraser University.

Cilia are found on cells throughout the body, from the retina of the eye to the nose, lung and kidneys, said Ou, who is first author on the study. A variety of human diseases have been shown to be directly linked to defects in cilia, he said. The structure of cilia has been preserved across hundreds of millions of years of evolution -- allowing researchers to study essentially the same genes in an animal as simple as the soil roundworm, Caenorhabditis elegans.


Scholey’s laboratory at the UC Davis Center for Genetics and Development uses the worms to directly observe the movement of motor proteins in cilia. The worms have cilia-coated cells in sensory pits near their mouths. Without functioning cilia, they lose their sense of smell.

The cilia are built and maintained by a system of motor proteins called kinesins that carry material from the base to the tip, walking along a protein microtubule. Two different kinesins, Kinesin-II and OSM-3, are required for efficient transport.

By studying worms lacking specific genes, the researchers showed that two genes associated with BBS, BBS-7 and BBS-8, and a third called DYF-1, allow the motor proteins to work together.

"They act as regulators of this subtle coordination," Scholey said.

The research is published in the July 28 issue of Nature.

Andy Fell | EurekAlert!
Further information:
http://www.ucdavis.edu

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