Abstract
Pheromones are neuronal signals that stimulate conspecific individuals to react to environmental stressors or stimuli. Research on the ascaroside (ascr) pheromones in Caenorhabditis elegans and other nematodes has made great progress since ascr#1 was first isolated and biochemically defined in 2005. In this review, we highlight the current research on the structural diversity, biosynthesis, and pleiotropic neuronal functions of ascr pheromones and their implications in animal physiology. Experimental evidence suggests that ascr biosynthesis starts with conjugation of ascarylose to very long-chain fatty acids that are then processed via peroxisomal β-oxidation to yield diverse ascr pheromones. We also discuss the concentration and stage-dependent pleiotropic neuronal functions of ascr pheromones. These functions include dauer induction, lifespan extension, repulsion, aggregation, mating, foraging and detoxification, among others. These roles are carried out in coordination with three G protein-coupled receptors that function as putative pheromone receptors: SRBC-64/66, SRG-36/37, and DAF-37/38. Pheromone sensing is transmitted in sensory neurons via DAF-16-regulated glutamatergic neurotransmitters. Neuronal peroxisomal fatty acid β-oxidation has important cell-autonomous functions in the regulation of neuroendocrine signaling, including neuroprotection. In the future, translation of our knowledge of nematode ascr pheromones to higher animals might be beneficial, as ascr#1 has some anti-inflammatory effects in mice. To this end, we propose the establishment of pheromics (pheromone omics) as a new subset of integrated disciplinary research area within chemical ecology for system-wide investigation of animal pheromones.
Highlights
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Pheromones are neuronal signaling molecules synthesized by various organisms and excreted into the environment, where they typically stimulate individuals of the same species to react to environmental changes [1,2]
Reports from several groups showed that there are robust changes in the expression levels of various genes in dauer larvae and dauer entry and exit [63,64,65,66]. These findings indicate that ascr pheromones exert their biological functions via some less-characterized signaling pathways involved in neuronal transmission [13,15,26]
Summary
Pheromones are neuronal signaling molecules synthesized by various organisms and excreted into the environment, where they typically stimulate individuals of the same species to react to environmental changes (e.g., temperature shifts, biological stimuli, or nutritional changes) [1,2]. TThhee cchheemmiiccaall ssttrruuccttuurree ooff ddaauummoonnee,, tthhee fifirrsstt cchhaarraacctteerriizzeedd aassccaarroossiiddee ((aassccrr)) pphheerroommoonnee ((aassccrr##11)),, ccoonnttaaiinnss aann aassccaarryylloossee ssuuggaarr aanndd aa mmeetthhyyllaatteedd sshhoorrtt--cchhaaiinn ffaattttyy aacciidd ((mmSSCCFFAA)) lliinnkkeedd bbyy aann ether bond [(2)-(6R)-(3,5-dihydroxy-6-methylteettrraahhyyddrrooppyyrraann--22--yyllooxxyy))hheeppttaannooiiccaacciidd]][[1133]]. They demonstrated that natural and chemically synthesized daumone could induce dauer ffoorrmmaattiioonnininththeewwildil-dt-ytpyepeC.Ce.leeglaegnasnlasbloarbaotroartyorsytrasitnra(iNn 2()Na2n)dainndCianenCorahenabodrhitaisbdbirtiigsgbsarieg. Some structural derivatives of ascr pheromones contain other functional groups (e.g., a methyl group, amino acid precursor, glucose, or benzoyl group) linked to the 2 - or 4 -position of the ascarylose moiety or to the 1 -position of the mSCFA moiety, generating a collection of highly diverse ascaroside structures (Figure 2). As most known ascr derivatives share a common structural backbone but differ in their mSCFA moieties or ascarylose modifications (Figure 2), determining their individual functions will be a daunting task
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