IFTA-2 is a conserved cilia protein involved in pathways regulating longevity and dauer formation in Caenorhabditis elegans.
Defects in cilia are associated with diseases and developmental abnormalities. Proper cilia function is required for sonic hedgehog and PDGFRalpha signaling in mammals and for insulin-like growth factor (IGF) signaling in Caenorhabditis elegans. However, the role of cilia in these pathways remains unknown. To begin addressing this issue, we are characterizing putative cilia proteins in C. elegans that are predicted to have regulatory rather than structural functions. In this report, we characterized the novel cilia protein T28F3.6 (IFTA-2, intraflagellar transport associated protein 2), which is homologous to the mammalian Rab-like 5 protein. We found that, unlike the intraflagellar transport (IFT) genes, disruption of ifta-2 does not result in overt cilia assembly abnormalities, nor did it cause chemotaxis or osmotic avoidance defects typical of cilia mutants. Rather, ifta-2 null mutants have an extended lifespan phenotype and are defective in dauer formation. Our analysis indicates that these phenotypes result from defects in the DAF-2 (insulin-IGF-1-like) receptor signaling pathway in ciliated sensory neurons. We conclude that IFTA-2 is not a ciliogenic protein but rather is a regulator of specific cilia signaling activities. Interestingly, a mammalian IFTA-2 homolog is also found in cilia, raising the possibility that its function has been conserved during evolution.
Schafer
Jenny C
JC
Department of Cell Biology, University of Alabama at Birmingham Medical Center, Birmingham, AL 35294, USA.
Winkelbauer
Marlene E
ME
Williams
Corey L
CL
Haycraft
Courtney J
CJ
Desmond
Renee A
RA
Yoder
Bradley K
BK
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D002923:Cilia / Q000235:genetics*; D017124:Conserved Sequence; D051858:Forkhead Transcription Factors; D008018:Life Cycle Stages; D008136:Longevity / Q000235:genetics*; D008954:Models, Biological; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000502:physiology; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D014018:Tissue Distribution; D014157:Transcription Factors / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; C515821:IFTA-2 protein, C elegans; D020691:rab GTP-Binding Proteins