Abstract
Over the past 10 years, the relevance of small-molecule signaling for many aspects of C. elegans development and behavior has become apparent. One prominent group of small-molecule signals are the ascarosides, which control dauer entry and exit as well as a variety of sex-specific and social behaviors, including male attraction, hermaphrodite repulsion, olfactory plasticity, and aggregation. This wide range of biological functions is facilitated by a great diversity of ascaroside chemical structures. These are based on the sugar ascarylose, which is linked to fatty acid-like side chains of varying lengths and often decorated further with building blocks derived from amino acids, folate, and other primary metabolites. Different ascarosides or combinations of ascarosides mediate different phenotypes, and even small differences in chemical structures are often associated with strongly altered activity profiles. Additional complexity arises from concentration-dependent effects and synergism between different ascarosides. The ascarosides are sensed by several types of chemosensory head neurons, including the ASK, ASI, and ADL neurons as well as the male-specific CEM neurons. Ascaroside perception is mediated by diverse families of G-protein coupled membrane receptors that act upstream of conserved signal transduction pathways, including insulin/IGF-1 signaling and transforming growth factor beta (TGF-β) signaling. Biosynthesis of the ascarosides appears to integrate input from several primary metabolic pathways, including peroxisomal β-oxidation of long-chain fatty acids and amino acid catabolism. Life stage, sex, as well as food availability and other environmental factors affect ascaroside biosynthesis, suggesting that ascaroside signaling communicates detailed information about life history and metabolic state.
Highlights
The term “ascarosides” was introduced originally to refer to a distinct type of lipid first detected in parasitic roundworms of the family Ascaridia more than 100 years ago
These very lipophilic ascarosides were shown to form a protective coating of Ascaris eggs, providing remarkable resilience to harsh environmental conditions and high concentrations of toxic or noxious chemicals (Fairbairn, 1957; Foor, 1967; Jezyk and Fairbairn, 1967)
A second group of fat storage mutants mapped to another gene, dhs-28, with strong sequence similarity to the dehydrogenase domain of mammalian peroxisomal multifunctional protein, which acts upstream of SCPx in mammalian peroxisomal β-oxidation. These results suggested that in C. elegans DHS-28 may act upstream of DAF-22 in peroxisomal β-oxidation and, given that daf-22 worms do not produce dauer pheromone, both DAF-22 and DHS-28 partake in ascaroside pheromone biosynthesis
Summary
The term “ascarosides” was introduced originally to refer to a distinct type of lipid first detected in parasitic roundworms of the family Ascaridia more than 100 years ago. Over the past seven years, a large number of more hydrophilic and structurally much more varied ascaroside derivates has been identified from C. elegans and other nematodes These hydrophilic ascarosides are important small-molecule signals that regulate a remarkable variety of biological processes in nematodes, including developmental timing, reproduction, and social signaling. In C. elegans, ascarosides were first identified as signaling molecules regulating the population density-dependent formation of dauer larvae. It became apparent that the dauer pheromone does not consist of just one or two compounds, but instead represents a complex mixture of ascarosides, in which some components act synergistically in dauer induction (Section 2.1) Following their identification as constituents of the dauer pheromone, it was discovered that ascarosides serve additional important signaling functions.
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