RRC ID 45900
著者 Zhang X, Feng L, Chinta S, Singh P, Wang Y, Nunnery JK, Butcher RA.
タイトル Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans.
ジャーナル Proc Natl Acad Sci U S A
Abstract 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 side-chain 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.
巻・号 112(13)
ページ 3955-60
公開日 2015-3-31
DOI 10.1073/pnas.1423951112
PII 1423951112
PMID 25775534
PMC PMC4386371
MeSH Acyl-CoA Oxidase / metabolism* Animals Caenorhabditis elegans / enzymology* Catalysis Chromatography, Liquid Mutation Oxygen / metabolism Pheromones / metabolism* Polymerase Chain Reaction Protein Multimerization Substrate Specificity Tandem Mass Spectrometry Temperature
IF 9.412
引用数 32
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm5192