Lifespan and dauer regulation by tissue-specific activities of Caenorhabditis elegans DAF-18.

Authors: Masse I; Molin L; Billaud M; Solari F

Abstract: 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.

Keywords: Animals; Animals, Genetically Modified; Caenorhabditis elegans/genetics/*growth & development/*physiology; Caenorhabditis elegans Proteins/genetics/*physiology; Gene Expression Regulation, Developmental; Genes, Helminth; Humans; Insulin/metabolism; Larva/growth & development; Longevity; Promoter Regions, Genetic; Receptor, Insulin/genetics/physiology; Recombinant Fusion Proteins/genetics/metabolism; Signal Transduction; Tissue Distribution; Transcription Factors/genetics/physiology
Journal: Developmental biology
Volume: 286
Issue: 1
Pages: 91-101
Date: Sept. 13, 2005
PMID: 16153634
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Masse I, Molin L, Billaud M, Solari F (2005) Lifespan and dauer regulation by tissue-specific activities of Caenorhabditis elegans DAF-18. Developmental biology 286: 91-101.

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