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Published on: February 4, 2014
Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant
1Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
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.
Insights
Complete absence of serotonin signaling in C. elegans mutants reveals its crucial role in regulating feeding, egg-laying, and fat storage, impacting metabolic control.
Area of Science:
- Neuroscience
- Genetics
- Metabolism
Background:
- Serotonin's functions are often studied using receptor-specific drugs, potentially missing broader effects due to compensatory receptor activity.
- Understanding the complete impact of serotonin signaling requires studying conditions with a total lack of the neurotransmitter.
Purpose of the Study:
- To investigate the behavioral and neuroendocrine consequences of a complete absence of serotonin signaling.
- To identify the key gene involved in serotonin biosynthesis in C. elegans.
Main Methods:
- Genome sequence analysis to identify the serotonin biosynthesis enzyme gene (tph-1).
- Generation and analysis of a tph-1 deletion mutant in C. elegans.
- Assessment of feeding rates, egg laying, fat storage, lifespan, and developmental arrest (dauer stage).
- Analysis of downstream neuroendocrine signaling pathways (TGF-β, insulin-like).
Main Results:
- A single tryptophan hydroxylase gene (tph-1) is essential for serotonin biosynthesis in C. elegans.
- tph-1 deletion mutants lack serotonin but are viable, exhibiting decreased feeding and egg laying.
- Mutants display increased fat storage, extended reproductive lifespan, and increased dauer formation.
- Metabolic dysregulation is linked to the downregulation of transforming growth factor-beta and insulin-like signaling.
Conclusions:
- The C. elegans serotonergic system plays a vital role in regulating feeding, reproduction, and metabolism.
- Absence of serotonin leads to significant metabolic dysregulation, partly mediated by TGF-β and insulin pathways.
- These findings highlight conserved roles of serotonergic systems in metabolic control, similar to mammals.
