A Novel Ascaroside Controls the Parasitic Life Cycle of the Entomopathogenic Nematode <i>Heterorhabditis bacteriophora</i>

Noguez, Jaime H.; Conner, Elizabeth S.; Zhou, Ya Jun; Ciche, Todd A.; Ragains, Justin R.; Butcher, Rebecca A.

doi:10.1021/cb300056q

Cited by 70 publications

(70 citation statements)

References 29 publications

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“…Using quantitative (q)RT-PCR, we show that acox-2 and acox-3, which act as gatekeepers for the production of shorter-chain ascarosides, are regulated by changes in temperature and food availability, leading to corresponding changes in ascaroside production. Studies of the ascaroside biosynthetic pathway and how it is modulated by different factors to control pheromone production will shed light on chemical communication in the C. elegans model system, as well as in other free-living and parasitic nematode species, which also use ascarosides as pheromones (22,23).…”

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confidence: 99%

Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

Zhang

Feng

Chinta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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158

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Caenorhabditis elegans uses ascaroside pheromones to induce development of the stress-resistant dauer larval stage and to coordinate various behaviors. Peroxisomal β-oxidation cycles are required for the biosynthesis of the fatty acid-derived side chains of the ascarosides. Here we show that three acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, form different protein homo-and heterodimers with distinct substrate preferences. Mutations in the acyl-CoA oxidase genes acox-1, -2, and -3 led to specific defects in ascaroside production. When the acyl-CoA oxidases were expressed alone or in pairs and purified, the resulting acyl-CoA oxidase homo-and heterodimers displayed different sidechain length preferences in an in vitro activity assay. Specifically, an ACOX-1 homodimer controls the production of ascarosides with side chains with nine or fewer carbons, an ACOX-1/ACOX-3 heterodimer controls the production of those with side chains with seven or fewer carbons, and an ACOX-2 homodimer controls the production of those with ω-side chains with less than five carbons. Our results support a biosynthetic model in which β-oxidation enzymes act directly on the CoA-thioesters of ascaroside biosynthetic precursors. Furthermore, we identify environmental conditions, including high temperature and low food availability, that induce the expression of acox-2 and/or acox-3 and lead to corresponding changes in ascaroside production. Thus, our work uncovers an important mechanism by which C. elegans increases the production of the most potent dauer pheromones, those with the shortest side chains, under specific environmental conditions. dauer | pheromone | ascaroside | beta-oxidation | acyl-CoA oxidase

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confidence: 99%

Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

Zhang

Feng

Chinta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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158

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“…Pheromones have been shown to exist in dozens of nematode species (8)(9)(10) and have been positively identified in several, including C. elegans (11)(12)(13)(14). Although HPLC-MS studies have led to the identification of more than 140 pheromones and pheromone-related metabolites in C. elegans (15), little is known about how production of such pheromones is regulated.…”

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confidence: 99%

Communication between oocytes and somatic cells regulates volatile pheromone production in Caenorhabditis elegans

Leighton

Choe

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Males of the androdioecious species Caenorhabditis elegans are more likely to attempt to mate with and successfully inseminate C. elegans hermaphrodites that do not concurrently harbor sperm. Although a small number of genes have been implicated in this effect, the mechanism by which it arises remains unknown. In the context of the battle of the sexes, it is also unknown whether this effect is to the benefit of the male, the hermaphrodite, or both. We report that successful contact between mature sperm and oocyte in the C. elegans gonad at the start of fertilization causes the oocyte to release a signal that is transmitted to somatic cells in its mother, with the ultimate effect of reducing her attractiveness to males. Changes in hermaphrodite attractiveness are tied to the production of a volatile pheromone, the first such pheromone described in C. elegans.fertilization | sex pheromones | egg-soma communication I ts properties of self-fertilization and rapid generation, along with its extensive library of mutants, make Caenorhabditis elegans an excellent system in which to study reproductive events. The generation time of C. elegans is under 3 d, and a single hermaphroditic worm can use its sperm to fertilize its own eggs, without the need for mating (1). C. elegans and related nematodes have a robust sperm sensation pathway that limits unfruitful oocyte maturation and ovulation (2). Both self-sperm and nonself-sperm secrete protein ligands, known as major sperm proteins (MSPs), that activate signal transduction pathways in both unfertilized oocytes, leading to activation of mitogen-activated protein kinase (MPK-1), and the somatic gonad, involving transcription factor CEH-18. The result of this signaling is the release of oocytes from prophase I arrest and the ovulation of unarrested oocytes into the uterus (3, 4).Several behaviors of female and hermaphroditic nematodes have been demonstrated to correlate with either the presence of sperm or the recentness of mating. C. elegans hermaphrodites that have exhausted their supply of self-sperm are more likely to elicit a mating response from males of their species, and less likely to resist an attempted mating. Mutant C. elegans hermaphrodites that develop without self-sperm also elicit more mating attempts, and this increase in attractiveness vanishes after a successful mating (5, 6). In the gonochoristic species Caenorhabditis brenneri and Caenorhabditis remanei, males are attracted to a volatile pheromone produced only by females that have not recently mated (7). The mechanisms that link these behaviors to sperm status remain unknown.Pheromones have been shown to exist in dozens of nematode species (8-10) and have been positively identified in several, including C. elegans (11-14). Although HPLC-MS studies have led to the identification of more than 140 pheromones and pheromone-related metabolites in C. elegans (15), little is known about how production of such pheromones is regulated. Life stage and environmental conditions have been shown to affect pheromone o...

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“…5). 54 In another example, sex-specific side chain hydroxylation in the sour past nematode Panagrellus redivivus results in formation of the male-specific dihydroxy ascaroside dhas#18, which acts as a female attractant (Fig. 5), whereas male attraction is modulated by the widely distributed ascr#1 (Fig.…”

Section: Ascaroside Signalling Is Highly Conserved In Nematodesmentioning

confidence: 99%

Combinatorial chemistry in nematodes: modular assembly of primary metabolism-derived building blocks

Reuß

Schroeder

2015

Nat. Prod. Rep.

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The nematode Caenorhabditis elegans was the first animal to have its genome fully sequenced and has become an important model organism for biomedical research. However, like many other animal model systems, its metabolome remained largely uncharacterized, until recent investigations demonstrated the importance of small molecule-based signalling cascades for virtually every aspect of nematode biology. These studies have revealed that nematodes are amazingly skilled chemists: using simple building blocks from conserved primary metabolism and a strategy of modular assembly, C. elegans and other nematode species create complex molecular architectures to regulate their development and behaviour. These nematode-derived modular metabolites (NDMMs) are based on the dideoxysugars ascarylose or paratose, which serve as scaffolds for attachment of moieties from lipid, amino acid, carbohydrate, citrate, and nucleoside metabolism. Mutant screens and comparative metabolomics based on NMR spectroscopy and MS have so-far revealed several 100 different ascarylose (“ascarosides”) and a few paratose (“paratosides”) derivatives, many of which represent potent signalling molecules that can be active at femtomolar levels, regulating development, behaviour, body shape, and many other life history traits. NDMM biosynthesis appears to be carefully regulated as assembly of different modules proceeds with very high specificity. Preliminary biosynthetic studies have confirmed the primary metabolism origin of some NDMM building blocks, whereas the mechanisms that underlie their highly specific assembly are not understood. Considering their functions and biosynthetic origin, NDMMs represent a new class of natural products that cannot easily be classified as “primary” or “secondary”. We believe that the identification of new variants of primary metabolism-derived structures that serve important signalling functions in C. elegans and other nematodes provides a strong incentive for a comprehensive re-analysis of metabolism in higher animals, including humans.

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A Novel Ascaroside Controls the Parasitic Life Cycle of the Entomopathogenic Nematode Heterorhabditis bacteriophora

Cited by 70 publications

References 29 publications

Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

Communication between oocytes and somatic cells regulates volatile pheromone production in Caenorhabditis elegans

Combinatorial chemistry in nematodes: modular assembly of primary metabolism-derived building blocks

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