Succinylated octopamine ascarosides and a new pathway of biogenic amine metabolism in Caenorhabditis elegans.
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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 HPLC-MS/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.
Chromatography, High Pressure Liquid
Published Version (Please cite this version)10.1074/jbc.C113.477000
Publication InfoArtyukhin, Alexander B; Yim, Joshua J; Srinivasan, Jagan; Izrayelit, Yevgeniy; Bose, Neelanjan; von Reuss, Stephan H; ... Schroeder, Frank C (2013). Succinylated octopamine ascarosides and a new pathway of biogenic amine metabolism in Caenorhabditis elegans. J Biol Chem, 288(26). pp. 18778-18783. 10.1074/jbc.C113.477000. Retrieved from https://hdl.handle.net/10161/11182.
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Associate Professor of Biology
We use the roundworm Caenorhabditis elegans as model to investigate how animals cope with fluctuations in food availability. We are interested in the signaling pathways and gene regulatory mechanisms that enable this worm to reversibly arrest development and endure starvation. We are interested in adaptation to nutrient stress over different time scalse, including nongenetic inheritance and multigenerational phenotypic plasticity.