Succinylated Octopamine Ascarosides and a New Pathway of Biogenic Amine Metabolism in Caenorhabditis elegans
Abstract
The ascarosides, small-molecule signals derived from combinatorial assembly of primary metabolism-derived building blocks, play a central role in Caenorhabditis elegans biology and regulate many aspects of development and behavior in this model organism as well as in other nematodes. Using HPLCMS/ MS-based targeted metabolomics, we identified novel ascarosides incorporating a side chain derived from succinylation of the neurotransmitter octopamine. These compounds, named osas#2, osas#9, and osas#10, are produced predominantly by L1 larvae, where they serve as part of a dispersal signal, whereas these ascarosides are largely absent from the metabolomes of other life stages. Investigating the biogenesis of these octopamine- derived ascarosides, we found that succinylation represents a previously unrecognized pathway of biogenic amine metabolism. At physiological concentrations, the neurotransmitters serotonin, dopamine, and octopamine are converted to a large extent into the corresponding succinates, in addition to the previously described acetates. Chemically, bimodal deactivation of biogenic amines via acetylation and succinylation parallels posttranslational modification of proteins via acetylation and succinylation of L-lysine. Our results reveal a small-molecule connection between neurotransmitter signaling and interorganismal regulation of behavior and suggest that ascaroside biosynthesis is based in part on co-option of degradative biochemical pathways.
Additional Information
© 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, April 12, 2013, and in revised form, May 13, 2013 Published, JBC Papers in Press, May 20, 2013. This work was supported in part by National Institutes of Health Grants GM088290 (to F. C. S.), GM008500 (to Y. I.), DK83593 (to L. A.), and GM085285 (to F. C. S. and P. W. S.), and National Science Foundation Grant IOS1120206 (to L. R. B.), as well as the Vassar College Mary Landon Sague Fellowship (to Y. I.). We thank Maciej Kukula for help with high resolution MS analysis.Attached Files
Published - J._Biol._Chem.-2013-Artyukhin-18778-83.pdf
Supplemental Material - jbc.C113.477000-1.pdf
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Additional details
- PMCID
- PMC3696653
- Eprint ID
- 39905
- Resolver ID
- CaltechAUTHORS:20130814-081450157
- NIH
- GM088290
- NIH
- GM008500
- NIH
- DK83593
- NIH
- GM085285
- NSF
- IOS1120206
- Vassar College Mary Landon Sague Fellowship
- Created
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2013-08-16Created from EPrint's datestamp field
- Updated
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2021-11-09Created from EPrint's last_modified field