Lifespan and dauer regulation by tissue-specific activities of Caenorhabditis elegans DAF-18.
In Caenorhabditis elegans, the insulin/IGF-1 DAF-2 receptor controls entry into dauer and longevity. DAF-2 signaling cascade includes the PI3 kinase homolog AGE-1 and the FOXO transcription factor DAF-16. The DAF-2 pathway is downregulated by DAF-18 which is encoded by the ortholog of the human tumor suppressor gene PTEN. We have previously shown that, like PTEN, DAF-18 antagonizes the activity of PI3 kinase/AGE-1. To further explore the role of DAF-18 in the regulation of the insulin pathway, we investigated which tissue(s) DAF-18 functions in to regulate dauer formation and lifespan. Our data show that complete dauer formation requires daf-18 expression in several tissues and that the remodeling of dauer tissues depends on both cell autonomous and cell nonautonomous daf-18 function(s). Conversely, daf-18 expression increases adult lifespan in all individual tissues tested. Furthermore, we show that the role of DAF-18 in dauer and lifespan control depends on DAF-16 activation, which is regulated by both cell autonomous and cell nonautonomous DAF-18 function(s) and in a tissue-specific manner. Overall, our data strongly suggest that several tissues act as signaling centers to mediate DAF-18 function and that DAF-18 could act outside the canonical DAF-2/DAF-16 pathway to regulate dauer and lifespan.
Masse
Ingrid
I
Laboratoire de Génétique Moléculaire, Signalisation et Cancer, CNRS UMR 5201, Université Claude Bernard Lyon 1, Domaine Rockefeller, 8 avenue Rockefeller, 69373 Cedex 08, Lyon, France.
Molin
Laurent
L
Billaud
Marc
M
Solari
Florence
F
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007814:Larva / Q000254:growth & development; D008136:Longevity; D011401:Promoter Regions, Genetic; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; C116661:DAF-18 protein, C elegans; D051858:Forkhead Transcription Factors; D007328:Insulin; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin