Abstract
Caenorhabditis elegans produces ascaroside pheromones to control its development and behavior. Even minor structural differences in the ascarosides have dramatic consequences for their biological activities. Here, we identify a mechanism that enables C. elegans to dynamically tailor the fatty-acid side chains of the indole-3-carbonyl (IC)-modified ascarosides it has produced. In response to starvation, C. elegans uses the peroxisomal acyl-CoA synthetase ACS-7 to activate the side chains of medium-chain IC-ascarosides for β-oxidation involving the acyl-CoA oxidases ACOX-1.1 and ACOX-3. This pathway rapidly converts a favorable ascaroside pheromone that induces aggregation to an unfavorable one that induces the stress-resistant dauer larval stage. Thus, the pathway allows the worm to respond to changing environmental conditions and alter its chemical message without having to synthesize new ascarosides de novo. We establish a new model for biosynthesis of the IC-ascarosides in which side-chain β-oxidation is critical for controlling the type of IC-ascarosides produced.
Highlights
We have shown that C. elegans attaches the IC head group to ascarosides with medium-length (8–11) side chains to generate aggregation pheromones such as ICasc-DC9 (Srinivasan et al, 2012)
Production of aggregation pheromones likely occurs under favorable environmental conditions such as food-rich conditions as C. elegans tends to aggregate on food (Srinivasan et al, 2012)
We have shown that C. elegans can activate IC-ascarosides with medium-length side chains for shortening of the side chains through b-oxidation to generate the dauer pheromone IC-asc-C5 (Figure 1B)
Summary
The nematode C. elegans secretes ascarosides as pheromones to induce development of the dauer larval stage at high population densities, as well as to control various behaviors, including male attraction to hermaphrodites, hermaphrodite attraction to males, avoidance, foraging behavior, and adult aggregation (Cassada and Russell, 1975; Golden and Riddle, 1982; Butcher et al, 2007; Butcher et al, 2008; Srinivasan et al, 2008; Butcher et al, 2009a; Pungaliya et al, 2009; Izrayelit et al, 2012; Srinivasan et al, 2012; Artyukhin et al, 2013; Greene et al, 2016). The exogenous addition of a synthetic ascaroside with a nine-carbon side chain, asc-C9 (ascr#10), to daf-22 worms (which are defective in b-oxidation and cannot make short- and medium-chain ascarosides, but which presumably can still biosynthesize the IC group and attach it) leads to production of the corresponding IC-ascaroside, IC-asc-C9 (icas#10) (von Reuss et al, 2012). Consistent with its function in activating ascarosides for peroxisomal b-oxidation, ACS-7 is localized to the peroxisome, rather than the lysosome, as previously reported by Panda et al Our results uncover the mechanism by which C. elegans responds to declining environmental conditions and converts aggregation-inducing, medium-chain IC-ascarosides to dauer-inducing, short-chain IC-ascarosides. C. elegans can efficiently alter the function of existing ascarosides by tailoring the length of the side chain, providing a novel strategy to rapidly modulate chemical signaling in response to environmental conditions
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