Location: Chemistry ResearchTitle: Density-based regulation of ascr#2 and ascr#4 expression in Caenorhabditis elegans) Author
Submitted to: Meeting Abstract
Publication Type: Abstract only
Publication Acceptance Date: 6/22/2011
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: The ascarosides are a family of nematode small molecules, many of which induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. For example, the male attracting pheromone is composed of a blend of at least four ascarosides, ascr#2, ascr#3, ascr#4 and ascr#8. Although many of the ascarosides have been shown to induce dauer formation at high concentrations, ascr#2 has been shown to be the most potent dauer-inducing compound. By using developmentally synchronized nematodes under starvation conditions we recently showed that ascr#2 content in growth media increased dramatically in conjunction with dauer formation. In addition to being a component of the mating pheromone, ascr#2 may also function as a density pheromone for C. elegans. In that case, its concentration in growth media would increase with increasing worm density. To test this hypothesis we grew nematodes in standard media and incubated at densities of 5000, 10000, 20000, 30000 and 40000 worms/ml in water for 1 h. Exudates were analyzed by LC-MS as previously described. As expected, total ascr#2 and ascr#4 content increased; however, ascr#2 release positively and ascr#4 release was negatively correlated with the increasing nematode density. Because ascr#2 is the non-glucosylated form of ascr#4, these data suggested that ascr#4 may be converted to ascr#2. Deuterium labeled ascr#2 or ascr#4 was incubated in water either with nematodes or nematode exudates. Labeled ascr#4 was converted to labeled ascr#2 wheras no ascr#2 was converted to ascr#4 in the presence of nematodes suggesting ascr#4 as a precursor of ascr#2. Furthermore, incubating ascr#4 with worm exudates did not result in conversion to ascr#2, suggesting that ascr#4-to-ascr#2 conversion does not happen in the media but instead after ascr#4-uptake by the worms. In conclusion, ascr#2 secretion per worm increases with increasing worm density, and this increase may in part result from enzymatic conversion of ascr#4 to ascr#2 by the worms. Ascr#4 might mainly function as an inactive form of low nutrients or high density “alarm pheromone”, easily converted to its active form by the nematodes. The function of ascr#4 or the ascr#2/ascr#4 ratio remains unknown. However, the conversion appears to be highly nematode specific, thus knowledge of enzymes that regulate production of nematode density pheromones may reveal new drug targets for controlling nematode parasites in humans and plants.