Genetics, Vol. 178, 157-169, January 2008, Copyright © 2008
doi:10.1534/genetics.107.079780

Regulation of Serotonin Biosynthesis by the G Proteins G_o and G_q Controls Serotonin Signaling in Caenorhabditis elegans

Jessica E. Tanis^*, James J. Moresco^,1, Robert A. Lindquist^,2 and Michael R. Koelle^,3

^* Department of Molecular, Cellular, and Developmental Biology, Department of Genetics and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520

³ Corresponding author: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, SHM CE30, New Haven, CT 06520-8024.
E-mail: michael.koelle{at}yale.edu

To analyze mechanisms that modulate serotonin signaling, we investigated how Caenorhabditis elegans regulates the function of serotonergic motor neurons that stimulate egg-laying behavior. Egg laying is inhibited by the G protein G_o and activated by the G protein G_q. We found that G_o and G_q act directly in the serotonergic HSN motor neurons to control egg laying. There, the G proteins had opposing effects on transcription of the tryptophan hydroxylase gene tph-1, which encodes the rate-limiting enzyme for serotonin biosynthesis. Antiserotonin staining confirmed that G_o and G_q antagonistically affect serotonin levels. Altering tph-1 gene dosage showed that small changes in tph-1 expression were sufficient to affect egg-laying behavior. Epistasis experiments showed that signaling through the G proteins has additional tph-1-independent effects. Our results indicate that (1) serotonin signaling is regulated by modulating serotonin biosynthesis and (2) G_o and G_q act in the same neurons to have opposing effects on behavior, in part, by antagonistically regulating transcription of specific genes. G_o and G_q have opposing effects on many behaviors in addition to egg laying and may generally act, as they do in the egg-laying system, to integrate multiple signals and consequently set levels of transcription of genes that affect neurotransmitter release.

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