HSF-1 is involved in regulation of ascaroside pheromone biosynthesis by heat stress in Caenorhabditis elegans

Abstract

The nematode worm Caenorhabditis elegans survives by adapting to environmental stresses such as temperature extremes by increasing the concentrations of ascaroside pheromones, termed ascarosides or daumones, which signal early C. elegans larvae to enter a non-aging dauer state for long-term survival. It is well known that production of ascarosides is stimulated by heat stress, resulting in enhanced dauer formation by which worms can adapt to environmental insults. However, the molecular mechanism by which ascaroside pheromone biosynthesis is stimulated by heat stress remains largely unknown. In the present study, we show that the heat-shock transcription factor HSF-1 can mediate enhanced ascaroside pheromone biosynthesis in response to heat stress by activating the peroxisomal fatty acid β-oxidation genes in C. elegans. To explore the potential molecular mechanisms, we examined the four major genes involved in the ascaroside biosynthesis pathway and then quantified the changes in both the expression of these genes and ascaroside production under heat-stress conditions. The transcriptional activation of ascaroside pheromone biosynthesis genes by HSF-1 was quite notable, which is not only supported by chromatin immunoprecipitation assays, but also accompanied by the enhanced production of chemically detectable major ascarosides (e.g. daumones 1 and 3). Consequently, the dauer formation rate was significantly increased by the ascaroside pheromone extracts from N2 wild-type but not from hsf-1(sy441) mutant animals grown under heat-stress conditions. Hence heat-stress-enhanced ascaroside production appears to be mediated at least in part by HSF-1, which seems to be important in adaptation strategies for coping with heat stress in this nematode.

Decoding chemical communication in nematodes

“…Environmental conditions (food availability and temperature), as well as larval stage and sex, have been shown to affect which ascarosides are produced by C. elegans . 6, 7, 26-28 It is unclear why the pheromones in C. elegans , such as the dauer pheromone and sex pheromone, consist of multiple ascaroside components. It has been speculated that for the dauer pheromone, in addition to population density, the different components of the dauer pheromone encode additional information about the status of conspecifics, such as their metabolic status, that helps to further inform the dauer decision.…”

“…Increased food availability leads to increased production of many of the ascarosides, although to varying degrees. 26, 28 In adults, shorter chain (ω-1)-ascarosides, such as the dauer pheromones asc-C6-MK (ascr#2) and IC-asc-C5 (icas#9), are not induced by food as much as other ascaroside pheromones. 26 Perhaps, this shift in ascaroside production enables the worm to produce a less potent dauer pheromone under well fed conditions.…”

Small-molecule pheromones and hormones controlling nematode development

“…Production of the ascarosides in C. elegans has been shown to be influenced by a variety of factors, including environmental conditions, such as food availability and temperature 33,61,68 , larval stage 69 , and sex 35 . Increased food availability tends to increase the production of most ascarosides, 61,68 and a dietary restricted mutant with reduced pharynx pumping produces less ascarosides.…”

“…Increased food availability tends to increase the production of most ascarosides, 61,68 and a dietary restricted mutant with reduced pharynx pumping produces less ascarosides. 68 Transcriptional regulation of the ACOX enzymes appears to affect the relative production of certain ascarosides.…”

“…Increased food availability tends to increase the production of most ascarosides, 61,68 and a dietary restricted mutant with reduced pharynx pumping produces less ascarosides. 68 Transcriptional regulation of the ACOX enzymes appears to affect the relative production of certain ascarosides. For example, bacterial food downregulates the expression of acox-1.3 in L4 larvae and suppresses the production of short-chain (ω-1)-ascarosides that lie downstream of ACOX-1.3, such as the dauer pheromone asc-C6-MK (ascr#2; C6) (Fig.…”