Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the intraflagellar transport machinery in sensory cilia.
The intraflagellar transport (IFT) machinery required to build functional cilia consists of a multisubunit complex whose molecular composition, organization, and function are poorly understood. Here, we describe a novel tryptophan-aspartic acid (WD) repeat (WDR) containing IFT protein from Caenorhabditis elegans, DYF-2, that plays a critical role in maintaining the structural and functional integrity of the IFT machinery. We determined the identity of the dyf-2 gene by transgenic rescue of mutant phenotypes and by sequencing of mutant alleles. Loss of DYF-2 function selectively affects the assembly and motility of different IFT components and leads to defects in cilia structure and chemosensation in the nematode. Based on these observations, and the analysis of DYF-2 movement in a Bardet-Biedl syndrome mutant with partially disrupted IFT particles, we conclude that DYF-2 can associate with IFT particle complex B. At the same time, mutations in dyf-2 can interfere with the function of complex A components, suggesting an important role of this protein in the assembly of the IFT particle as a whole. Importantly, the mouse orthologue of DYF-2, WDR19, also localizes to cilia, pointing to an important evolutionarily conserved role for this WDR protein in cilia development and function.
Efimenko
Evgeni
E
Karolinska Institute, Department of Biosciences and Nutrition, Södertörn University College, School of Life Sciences, S-14189 Huddinge, Sweden.
Blacque
Oliver E
OE
Ou
Guangshuo
G
Haycraft
Courtney J
CJ
Yoder
Bradley K
BK
Scholey
Jonathan M
JM
Leroux
Michel R
MR
Swoboda
Peter
P
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D005091:Exons / Q000235:genetics; D005407:Flagella / Q000378:metabolism*; D005453:Fluorescence; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017238:Genes, Helminth / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017385:Sequence Homology; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C516176:DYF-2 protein, C elegans; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C486869:WDR19 protein, human