Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant.
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.
Sze
J Y
JY
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Victor
M
M
Loer
C
C
Shi
Y
Y
Ruvkun
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D005247:Feeding Behavior; D017353:Gene Deletion; D015801:Helminth Proteins / Q000378:metabolism; D008136:Longevity; D008969:Molecular Sequence Data; D012098:Reproduction; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D015801:Helminth Proteins; D013002:Somatomedins; D016212:Transforming Growth Factor beta; D012701:Serotonin; D014365:Tryptophan Hydroxylase