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RESEARCH PAPER
1 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada; 2 Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA; 3 Department of Biological Sciences, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada; 4 Institute of Genetic Medicine and 5 Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA; 6 Molecular Medicine Unit, Institute of Child Health, University College London, London WC1 1EH, UK; 7 The Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.
[Keywords: Bardet-Biedl syndrome; BBS proteins; cilia and flagella; Caenorhabditis elegans; basal body; intraflagellar transport]
Received February 13, 2004; revised version accepted April 30, 2004.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1194004.
8 Corresponding author. E-MAIL leroux{at}sfu.ca; FAX: (604) 291-5583.
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