Eight proteins, defects in which are associated with Meckel-Gruber syndrome and nephronophthisis ciliopathies, work together as two functional modules at the transition zone to establish basal body/transition zone connections with the membrane and barricade entry of non-ciliary components into this organelle.

Cilia and flagella play important roles in many physiological processes, including cell and fluid movement, sensory perception, and development. The biogenesis and maintenance of cilia depend on intraflagellar transport (IFT), a motility process that operates bidirectionally along the ciliary axoneme. Disruption in IFT and cilia function causes several human disorders, including polycystic kidneys, retinal dystrophy, neurosensory impairment, and Bardet-Biedl syndrome (BBS). To uncover new ciliary components, including IFT proteins, we compared C. elegans ciliated neuronal and nonciliated cells through serial analysis of gene expression (SAGE) and screened for genes potentially regulated by the ciliogenic transcription factor, DAF-19. Using these complementary approaches, we identified numerous candidate ciliary genes and confirmed the ciliated-cell-specific expression of 14 novel genes. One of these, C27H5.7a, encodes a ciliary protein that undergoes IFT. As with other IFT proteins, its ciliary localization and transport is disrupted by mutations in IFT and bbs genes. Furthermore, we demonstrate that the ciliary structural defect of C. elegans dyf-13(mn396) mutants is caused by a mutation in C27H5.7a. Together, our findings help define a ciliary transcriptome and suggest that DYF-13, an evolutionarily conserved protein, is a novel core IFT component required for cilia function.

The non-motile cilium, once believed to be a vestigial cellular structure, is now increasingly associated with the ability of a wide variety of cells and organisms to sense their chemical and physical environments. With its limited number of sensory cilia and diverse behavioral repertoire, C. elegans has emerged as a powerful experimental system for studying how cilia are formed, function, and ultimately modulate complex behaviors. Here, we discuss the biogenesis, distribution, structures, composition and general functions of C. elegans cilia. We also briefly highlight how C. elegans is being used to provide molecular insights into various human ciliopathies, including Polycystic Kidney Disease and Bardet-Biedl Syndrome. Albert, P.S., Brown, S.J., and Riddle, D.L. (1981). Sensory control of dauer larva formation in Caenorhabditis elegans. J. Comp. Neurol. 198, 435-451. Abstract Article N. (2003). Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature 425, 628-633. Abstract Article Apfeld, J., and Kenyon, C. (1999). Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402, 804-809. Abstract Article The sensory cilia of Caenorhabditis elegans References

No abstract

The assembly and maintenance of cilia require intraflagellar transport (IFT), a microtubule-dependent bidirectional motility of multisubunit protein complexes along ciliary axonemes. Defects in IFT and the functions of motile or sensory cilia are associated with numerous human ailments, including polycystic kidney disease and Bardet-Biedl syndrome. Here, we identify a novel Caenorhabditis elegans IFT gene, IFT-associated gene 1 (ifta-1), which encodes a WD repeat-containing protein with strong homology to a mammalian protein of unknown function. Both the C. elegans and human IFTA-1 proteins localize to the base of cilia, and in C. elegans, IFTA-1 can be observed to undergo IFT. IFTA-1 is required for the function and assembly of cilia, because a C. elegans ifta-1 mutant displays chemosensory abnormalities and shortened cilia with prominent ciliary accumulations of core IFT machinery components that are indicative of retrograde transport defects. Analyses of C. elegans IFTA-1 localization/motility along bbs mutant cilia, where anterograde IFT assemblies are destabilized, and in a che-11 IFT gene mutant, demonstrate that IFTA-1 is closely associated with the IFT particle A subcomplex, which is implicated in retrograde IFT. Together, our data indicate that IFTA-1 is a novel IFT protein that is required for retrograde transport along ciliary axonemes. INTRODUCTIONCilia and flagella are highly conserved cellular appendages found on many, if not most, mammalian cell types as well as on cells of countless multi-and unicellular lower eukaryotes, including Caenorhabditis elegans and Chlamydomonas reinhardtii. Cilia are grossly characterized as motile (e.g., Chlamydomonas flagella) or nonmotile (e.g., primary cilia of mammals and C. elegans). Motile cilia enable fluid/cell movement, whereas nonmotile cilia are implicated in sensory processes such as olfaction, chemosensation, mechanosensation, and photoreception (Davenport and Yoder, 2005). The physiological importance of cilia function is highlighted by the existence of numerous human ciliopathies, including polycystic kidney disease, nephronophthisis, retinal dystrophy, organ laterality defects, and phenotypically complex disorders such as Bardet-Biedl syndrome (BBS), Alström syndrome, and Meckel syndrome (Ansley et al., 2003;Otto et al., 2003;Afzelius, 2004;Pazour, 2004;Hearn et al., 2005;Kyttala et al., 2006;Smith et al., 2006).The assembly and maintenance of the microtubule-dependent cilia and flagella structures depends on intraflagellar transport (IFT). Initially described in Chlamydomonas flagella, IFT is a bidirectional motility of multisubunit protein complexes, which deliver various cargo proteins that serve to build and maintain the structure and function of cilia and flagella (Kozminski et al., 1993;Rosenbaum and Witman, 2002;Scholey 2003). Anterograde IFT from the basal body, at the base of cilia, to the distal ciliary tip is driven by microtubule plus-ended kinesin-2 motors (Cole et al., 1993;Signor et al., 1999a;Snow et al., 2004), and an IFT-dynein motor ...