Abstract
The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts). The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1) that is the catalytic subunit of the major N alpha-acetyltransferase (NatA). A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO) DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.
Highlights
Animal development is a complex process that involves hierarchical gene regulatory networks and is influenced by environmental conditions
We show that overexpression of our newly discovered protein stimulates the transcriptional activity of DAF-16
It is possible that abnormal DAF-31 activity may lead to tumor growth by reducing DAF-16 activity
Summary
Animal development is a complex process that involves hierarchical gene regulatory networks and is influenced by environmental conditions. At least three environmental cues have been defined: food supply, temperature, and a constitutively secreted dauer-inducing pheromone that signals population density [2]. The L2 larva is developmentally committed to continued growth, whereas the L2d larva can molt to a dauer larva if food is scarce and the animals are overcrowded, or to an L3 larva should conditions improve. Three functionally overlapping neural pathways control the developmental response to environmental cues. They involve DAF-7/TGF-ß [6,7], DAF-11/cyclic GMP [8], and DAF2/insulin-like [9,10] pathways, which relay the environmental signals to a nuclear hormone receptor, DAF-12 [11], to control dauer versus non-dauer morphogenesis
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