Modulation of Serotonin-Controlled Behaviors by G _o in Caenorhabditis elegans

Abstract

Seven transmembrane receptors and their associated heterotrimeric guanine nucleotide-binding proteins (G proteins) have been proposed to play a key role in modulating the activities of neurons and muscles. The physiological function of the Caenorhabditis elegans G protein Go has been genetically characterized. Mutations in the goa-1 gene, which encodes an alpha subunit of Go (G alpha o), cause behavioral defects similar to those observed in mutants that lack the neurotransmitter serotonin (5-HT), and goa-1 mutants are partially resistant to exogenous 5-HT. Mutant animals that lack G alpha o and transgenic animals that overexpress G alpha o [goa-1(xs) animals] have reciprocal defects in locomotion, feeding, and egg laying behaviors. In normal animals, all of these behaviors are regulated by 5-HT. These results demonstrate that the level of Go activity is a critical determinant of several C. elegans behaviors and suggest that Go mediates many of the behavioral effects of 5-HT.

G o α regulates olfactory adaptation by antagonizing G q α-DAG signaling in Caenorhabditis elegans

“…As in mammals, GOA-1 G o ␣ is ubiquitously expressed in the nervous system in C. elegans and reported to be involved in many aspects of behavior (21,22). In our study, we demonstrated that GOA-1 modulates sensory responses, specifically, olfactory adaptation (and salt chemotaxis plasticity) in C. elegans.…”

“…However, the mode of action of G o in these behaviors is unclear. C. elegans has 21 G protein ␣-subunit genes (19,20), and the only orthologue of mammalian G o ␣ is encoded by the goa-1 gene (21,22). Mutations in goa-1 cause various defects in behaviors, including locomotion and egg laying.…”

“…The stimulation of EGL-30 causes a rise of diacylglycerol (DAG) level through activation of EGL-8 PLC␤, leading to a change in distribution of UNC-13, resulting in facilitation of acetylcholine release at neuromuscular junctions (25,26). By contrast, GOA-1 is known to negatively regulate the EGL-30 and DAG signaling pathway in response to serotonin (22, 27) or dopamine (28).To understand how G o ␣ modulates olfactory responses, genetic approaches were taken in this study in C. elegans. We found that GOA-1 G o ␣ is required for adaptation to AWC-sensed odorants.…”

Potential roles of heterotrimeric G proteins of the endomembrane system

“…One possible explanation for the observed specificity of heterotrimer subunit composition is a compartmentalization of the signal transduction elements in the plasma membrane of intact cells [26]. Nevertheless, the G~o subunit is currently without a specific effector-regulating function, though results obtained from modulating gene expression of the G~o gene in the roundworm Caenorhabditis elegans underline an important role of this G protein in various neuronal functions [51,52].…”

Are Caenorhabditis elegans receptors useful targets for drug discovery: Pharmacological comparison of tyramine receptors with high identity from C. elegans (TYRA-2) and Brugia malayi (Bm4)

“…In general, TA/OA oppose the action of serotonin (5-HT) [1]. For example, in the free-living nematode, Caenorhabditis elegans, exogenous TA or OA cause hyperactivity, inhibit pharyngeal pumping on bacteria or 5-HT and suppress 5-HT stimulated egg-laying [2][3][4]. The OA inhibition of pumping appears to involve Gα o , as OA inhibits the firing rate of the pharyngeal muscle in wild-type C. elegans, but has no effect on goa-1 mutants defective for Gα o function [5].…”