Advertisement

Caenorhabditis elegans as a Model Organism for Ciliopathies and Related Forms of Photoreceptor Degeneration

  • Calvin A. Mok
  • Elise HéonEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

Ciliopathies are a growing class of potentially pleiotropic disorders involving defective function, maintenance or biogenesis of primary cilia. Of the numerous features involved, photoreceptor degeneration is often reported and is a primary feature of Bardet–Biedl syndrome (OMIM #209900) and other ciliopathies such as Leber’s congenital amaurosis and Senior–Løken syndrome. A number of animal models ranging from Chlamydomonas reinhardtii to Caenorhabditis elegans, to Mus musculus have helped to elucidate the possible molecular functions of BBS proteins among other ciliopathies. Using BBS as a disease model, we assessed the possible roles of BBS proteins in intraflagellar transport, protein regulation and vesicle transport using C. elegans as a model of phototransduction and cilia-related retinopathies.

Keywords

Bardet–Biedl syndrome C. elegans Photoreceptor degeneration Primary cilia Ciliopathy Model organism 

References

  1. Baker K, Beales PL (2009) Making sense of cilia in disease: the human ciliopathies. Am J Med Genet C Semin Med Genet 151C:281–295PubMedCrossRefGoogle Scholar
  2. Beales PL, Warner AM, Hitman GA et al (1997) Bardet-Biedl syndrome: a molecular and phenotypic study of 18 families. J Med Genet 34:92–98PubMedCrossRefGoogle Scholar
  3. Blacque OE, Reardon MJ, Li C et al (2004) Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev 18:1630–1642PubMedCrossRefGoogle Scholar
  4. Corbit KC, Aanstad P, Singla V et al (2005) Vertebrate Smoothened functions at the primary cilium. Nature 437:1018–1021PubMedCrossRefGoogle Scholar
  5. Corbit KC, Shyer AE, Dowdle WE et al (2008) Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol 10:70–76PubMedCrossRefGoogle Scholar
  6. Evans JE, Snow JJ, Gunnarson AL et al (2006) Functional modulation of IFT kinesins extends the sensory repertoire of ciliated neurons in Caenorhabditis elegans. J Cell Biol 172:663–669PubMedCrossRefGoogle Scholar
  7. Huangfu D, Liu A, Rakeman AS et al (2003) Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426:83–87PubMedCrossRefGoogle Scholar
  8. Inglis PN, Boroevich KA, Leroux MR (2006) Piecing together a ciliome. Trends Genet 22:491–500PubMedCrossRefGoogle Scholar
  9. Jin H, White SR, Shida T et al (2010) The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell 141:1208–1219PubMedCrossRefGoogle Scholar
  10. Jones C, Roper VC, Foucher I et al (2008) Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat Genet 40:69–77PubMedCrossRefGoogle Scholar
  11. Lai CH, Chou CY, Ch’ang LY et al (2000) Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome Res 10:703–713PubMedCrossRefGoogle Scholar
  12. Lechtreck KF, Johnson EC, Sakai T et al (2009) The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of specific signaling proteins from flagella. J Cell Biol 187:1117–1132PubMedCrossRefGoogle Scholar
  13. Lin F, Hiesberger T, Cordes K et al (2003) Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc Natl Acad Sci USA 100:5286–5291PubMedCrossRefGoogle Scholar
  14. Liu J, Ward A, Gao J et al (2010) C. elegans phototransduction requires a G protein-dependent cGMP pathway and a taste receptor homolog. Nat Neurosci 13:715–722PubMedCrossRefGoogle Scholar
  15. Loktev AV, Zhang Q, Beck JS et al (2008) A BBSome subunit links ciliogenesis, microtubule stability, and acetylation. Dev Cell 15:854–865PubMedCrossRefGoogle Scholar
  16. Marshall WF, Nonaka S (2006) Cilia: tuning in to the cell’s antenna. Curr Biol 16:R604–614PubMedCrossRefGoogle Scholar
  17. McMahon HT, Mills IG (2004) COP and clathrin-coated vesicle budding: different pathways, common approaches. Curr Opin Cell Biol 16:379–391PubMedCrossRefGoogle Scholar
  18. Ou G, Blacque OE, Snow JJ et al (2005) Functional coordination of intraflagellar transport motors. Nature 436:583–587PubMedCrossRefGoogle Scholar
  19. Pan X, Ou G, Civelekoglu-Scholey G et al (2006) Mechanism of transport of IFT particles in C. elegans cilia by the concerted action of kinesin-II and OSM-3 motors. J Cell Biol 174:1035–1045PubMedCrossRefGoogle Scholar
  20. Rohatgi R, Milenkovic L, Scott MP (2007) Patched1 regulates hedgehog signaling at the primary cilium. Science 317:372–376PubMedCrossRefGoogle Scholar
  21. Ross AJ, May-Simera H, Eichers ER et al (2005) Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 37:1135–1140PubMedCrossRefGoogle Scholar
  22. Stagg SM, LaPointe P, Balch WE (2007) Structural design of cage and coat scaffolds that direct membrane traffic. Curr Opin Struct Biol 17:221–228PubMedCrossRefGoogle Scholar
  23. Tobin JL, Beales PL (2009) The nonmotile ciliopathies. Genet Med 11:386–402PubMedCrossRefGoogle Scholar
  24. Ward A, Liu J, Feng Z et al (2008) Light-sensitive neurons and channels mediate phototaxis in C. elegans. Nat Neurosci 11:916–922PubMedCrossRefGoogle Scholar
  25. Zaghloul NA, Katsanis N (2009) Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy. J Clin Invest 119:428–437PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.The Program in Genetics and Genome BiologyThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Samuel Lunenfeld Research InstituteMount Sinai HospitalTorontoCanada
  3. 3.Department of Ophthalmology and Vision SciencesThe Hospital for Sick ChildrenTorontoCanada

Personalised recommendations