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

Ji Ying Sze, Martin Victor, Curtis Loer, Yang Shi, Gary Ruvkun

Research output: Contribution to journalArticle

403 Citations (Scopus)

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-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 obesity.

Original languageEnglish (US)
Pages (from-to)560-564
Number of pages5
JournalNature
Volume403
Issue number6769
DOIs
StatePublished - Feb 3 2000
Externally publishedYes

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Caenorhabditis elegans
Serotonin
Food
Tryptophan Hydroxylase
Sequence Deletion
Serotonin Receptors
Transforming Growth Factors
Ovum
Down-Regulation
Obesity
Eating
Fats
Genome
Insulin
Enzymes
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • General

Cite this

Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. / Sze, Ji Ying; Victor, Martin; Loer, Curtis; Shi, Yang; Ruvkun, Gary.

In: Nature, Vol. 403, No. 6769, 03.02.2000, p. 560-564.

Research output: Contribution to journalArticle

Sze, Ji Ying ; Victor, Martin ; Loer, Curtis ; Shi, Yang ; Ruvkun, Gary. / Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. In: Nature. 2000 ; Vol. 403, No. 6769. pp. 560-564.
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