Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

  1. Oliver E. Blacque1,
  2. Michael J. Reardon2,
  3. Chunmei Li1,
  4. Jonathan McCarthy1,
  5. Moe R. Mahjoub3,
  6. Stephen J. Ansley4,
  7. Jose L. Badano4,
  8. Allan K. Mah1,
  9. Philip L. Beales6,
  10. William S. Davidson1,
  11. Robert C. Johnsen1,
  12. Mark Audeh2,
  13. Ronald H.A. Plasterk7,
  14. David L. Baillie1,
  15. Nicholas Katsanis4,5,
  16. Lynne M. Quarmby3,
  17. Stephen R. Wicks2, and
  18. Michel R. Leroux1,8
  1. 1Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada; 2Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA; 3Department of Biological Sciences, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada; 4Institute of Genetic Medicine and 5Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA; 6Molecular Medicine Unit, Institute of Child Health, University College London, London WC1 1EH, UK; 7The Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands

Abstract

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

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • 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.

    • Accepted April 30, 2004.
    • Received February 13, 2004.
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  1. doi: 10.1101/gad.1194004 Genes & Dev. 18: 1630-1642 Cold Spring Harbor Laboratory Press

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