Food and Metabolic Signalling Defects in a Caenorhabditis Elegans Serotonin-Synthesis Mutant

Nature. 2000 Feb 3;403(6769):560-4. doi: 10.1038/35000609.

Abstract

The functions of serotonin have been assigned through serotonin-receptor-specific drugs and mutants; 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 transforming growth factor-beta 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 obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Behavior, Animal
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins*
  • Feeding Behavior
  • Gene Deletion
  • Helminth Proteins / metabolism
  • Longevity
  • Molecular Sequence Data
  • Reproduction
  • Serotonin / physiology*
  • Signal Transduction
  • Somatomedins / metabolism
  • Transforming Growth Factor beta / metabolism
  • Tryptophan Hydroxylase / genetics
  • Tryptophan Hydroxylase / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • DAF-7 protein, C elegans
  • Helminth Proteins
  • Somatomedins
  • Transforming Growth Factor beta
  • Serotonin
  • Tryptophan Hydroxylase