Succinylated Octopamine Ascarosides and a New Pathway of Biogenic Amine Metabolism in Caenorhabditis elegans

Artyukhin, Alexander B.; Yim, Joshua J.; Srinivasan, Jagan; Izrayelit, Yevgeniy; Bose, Neelanjan; Reuß, Stephan H. von; Jo, Yeara; Jordan, James M.; Baugh, L. Ryan; Cheong, Mi Cheong; Sternberg, Paul W.; Avery, Leon; Schroeder, Frank C.

doi:10.1074/jbc.c113.477000

Cited by 75 publications

(116 citation statements)

References 36 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Starvation has been suggested to increase the ratio of asc-ΔC9 to asc-ωC3 in longterm, mixed-stage cultures (11). On the other hand, starved L1 larvae, in comparison with those that are fed, have been shown to secrete a higher ratio of ascarosides with shorter, 5-carbon side chains to those with longer, 9-carbon side chains (12).…”

mentioning

confidence: 99%

“…Dauers have a thickened cuticle, do not feed, derive energy from fat stores, and up-regulate stress-resistance pathways (6). Certain ascarosides also influence behaviors, including male attraction to hermaphrodites, hermaphrodite attraction to males, avoidance, and aggregation (7)(8)(9)(10)(11)(12). C. elegans senses the ascarosides using several classes of G protein-coupled receptors (GPCRs), which are expressed in specific chemosensory neurons (13,14).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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.

158

View full text Add to dashboard Cite

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

show abstract

mentioning

confidence: 99%

mentioning

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.

158

View full text Add to dashboard Cite

show abstract

“…C. elegans possess similar capabilities for homoserine lactone AIs (20). Recently, Artyukhin et al (49) suggested that molecules with short carbon chains act as dispersal signals for C. elegans, whereas molecules with longer carbon chains may signal that there is sufficient nutrition in the environment. This suggestion is consistent with our observation that bacterialproduced molecules containing short carbon chains were either neutral or repulsive in chemotaxis assays, whereas longer chain molecules were attractants (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…For example, while many of the nematode genes involved in dauer formation have been characterized, C. elegans uses an unknown bacterial cue or cues to exit the metabolically arrested dauer phase and continue through development (43). Similarly, in a recent characterization of L1 nematode metabolites, it was found that the C. elegans avoidance response to L1-produced small molecules is overridden by the addition of bacteria to the assay (49). In these cases of bacterial-regulated C. elegans development and behavior, the specific bacterial-produced stimuli remain mysterious.…”

Section: Discussionmentioning

confidence: 99%

“…Small molecules control dauer formation, chemoavoidance, and chemoattraction. In each case the molecules are detected by distinct neural cells (30); nonetheless, each behavior appears to be differentially influenced by the length of the carbon chain on the small molecule (47)(48)(49). Possibly, sensory neuron subtypes distinguish molecules, at least in part, based on carbon chain length.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Caenorhabditis elegans Recognizes a Bacterial Quorum-sensing Signal Molecule through the AWCON Neuron

Werner

Perez

Ghosh

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The nematode Caenorhabditis elegans consumes bacteria as its sole food source. Results: The bacterium Vibrio cholerae produces a quorum-sensing signal molecule called CAI-1, which C. elegans detects through the AWC ON chemosensory neuron. Conclusion: C. elegans uses bacterial-produced molecules as cues, and these molecules are also physiologically significant to bacteria. Significance: The V. cholerae molecule CAI-1 enables cross-kingdom chemical interaction.

show abstract

Biosynthesis of Modular Ascarosides in C. elegans

et al. 2017

Self Cite

View full text Add to dashboard Cite

The nematode Caenorhabditis elegans uses simple building blocks from primary metabolism and as trategy of modular assembly to build ag reat diversity of signaling molecules,t he ascarosides,w hichf unction as ac hemical language in this model organism. In the ascarosides,t he dideoxysugar ascarylose serves as as caffold to which diverse moieties from lipid, amino acid, neurotransmitter,and nucleoside metabolism are attached. However,t he mechanisms that underlie the highly specific assembly of ascarosides are not understood. We show that the acyl-CoA synthetase ACS-7, which localizes to lysosome-related organelles,i ss pecifically required for the attachment of different building blocks to the 4'-position of ascr#9. We further showt hat mutants lacking lysosome-related organelles are defective in the production of all 4'-modified ascarosides,thus identifying the waste disposal system of the cell as ahotspot for ascaroside biosynthesis.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: http://dx.

show abstract

Succinylated Octopamine Ascarosides and a New Pathway of Biogenic Amine Metabolism in Caenorhabditis elegans

Cited by 75 publications

References 36 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

Caenorhabditis elegans Recognizes a Bacterial Quorum-sensing Signal Molecule through the AWCON Neuron

Biosynthesis of Modular Ascarosides in C. elegans

Contact Info

Product

Resources

About