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.

The endoplasmic reticulum (ER) is divided into rough and smooth domains (RER and SER). The two domains share most proteins, but RER is enriched in some membrane proteins by an unknown mechanism. We studied RER protein targeting by expressing fluorescent protein fusions to ER membrane proteins in Caenorhabditis elegans. In several cell types RER and general ER proteins colocalized, but in neurons RER proteins were concentrated in the cell body, whereas general ER proteins were also found in neurites. Surprisingly RER membrane proteins diffused rapidly within the cell body, indicating they are not localized by immobilization. Ribosomes were also concentrated in the cell body, suggesting they may be in part responsible for targeting RER membrane proteins.

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