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Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant

Nature volume 403, pages 560–564 (2000)Cite this article

Abstract

The functions of serotonin have been assigned through serotonin-receptor-specific drugs and mutants1,2; however, because a constellation of receptors remains when a single receptor subtype is inhibited, the coordinate responses to modulation of serotonin levels may be missed. Here we report the analysis of behavioural and neuroendocrine defects caused by a complete lack of serotonin signalling. Analysis of the C. elegans genome sequence showed that there is a single tryptophan hydroxylase gene (tph-1)—the key enzyme for serotonin biosynthesis. Animals bearing a tph-1 deletion mutation do not synthesize serotonin but are fully viable. The tph-1 mutant shows abnormalities in behaviour and metabolism that are normally coupled with the sensation and ingestion of food: rates of feeding and egg laying are decreased; large amounts of fat are stored; reproductive lifespan is increased; and some animals arrest at the metabolically inactive dauer stage. This metabolic dysregulation is, in part, due to downregulation of tranforming growth factor-β and insulin-like neuroendocrine signals. The action of the C. elegans serotonergic system in metabolic control is similar to mammalian serotonergic input to metabolism and obesity2.

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Figure 1: tph-1 encodes a tryptophan hydroxylase.
Figure 2: tph-1 is expressed in serotonergic neurons.
Figure 3: tph-1(mg280) affects food-modulated behaviours, metabolism and reproductive longevity.
Figure 4: Metabolic defects in tph-1(mg280) animals.

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Acknowledgements

We thank P. Sternberg, S. Nurrish and J. Kaplan for advice on serotonin regulation of behaviour; members of the Ruvkun lab for critical reading of the manuscript. R. Lee for help with graphics; G. Sandoval for some strain characterizations; A. Lander for advice on his microscope and software, and especially R. Lints and S. Emmons for analysing the dopamine accumulation in tph-1(mg280). J.Y.S. was supported by a fellowship from the National Institutes of Health, M.V. by a fellowship from the DAAD German Academic Exchange Service, C.M.L. by NSF. This work was supported by grants from Hoechst AG to G.R., and grants from NIH to Y.S. Some nematode strains were supplied by the Caenorhabditis Genetics Center supported by the NIH and the University of Minnesota.

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Author notes

  1. Ji Ying Sze

    Present address: Department of Anatomy and Neurobiology, College of Medicine, University of California, Irvine, California, 92697-1280, USA

Authors and Affiliations

  1. Department of Molecular Biology, Department of Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Ji Ying Sze & Gary Ruvkun

  2. Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Martin Victor & Yang Shi

  3. Department of Biology, University of San Diego, San Diego, 92110, California, USA

    Curtis Loer

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Correspondence to Gary Ruvkun.

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Sze, J., Victor, M., Loer, C. et al. Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. Nature 403, 560–564 (2000). https://doi.org/10.1038/35000609

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