Activation of EGL-47, a Gα_o-coupled receptor, inhibits function of hermaphrodite-specific motor neurons to regulate Caenorhabditis elegans egg-laying behavior

Caenorhabditis elegans egg-laying behavior is inhibited by neurotransmitter signaling through the neural G-protein Gα_o and serves as a model for analyzing Gα_o signaling. Mutations that alter egg-laying frequency have identified genes encoding a number of signaling proteins that act with Gα_o, but the receptors that activate Gα_o remain mostly uncharacterized. To further analyze Gα_o signaling, we cloned the egl-47 gene, which was identified by two dominant mutations that severely inhibit egg laying, egl-47 encodes two orphan G-protein-coupled receptor isoforms, which share all seven transmembrane domains but have different extracellular N termini. Both dominant mutations change the same alanine to valine in the sixth transmembrane domain, resulting in constitutively activated receptors. Deletion of the egl-47 gene caused no detectable egg-laying defects, suggesting that EGL-47 functions redundantly, or it inhibits egg laying under specific circumstances as yet unidentified. Using promoter::green fluorescent protein transgenes, we found that EGL-47 is expressed in a number of neurons, including the hermaphrodite-specific neurons (HSNs) that innervate the egg-laying muscles to stimulate contraction. Transgenic expression of constitutively active EGL-47 or constitutively active Gα_o specifically in the HSNs was sufficient to inhibit egg-laying behavior. Our results suggest that EGL-47 regulates egg laying by activating Gα_o in the HSN motor neurons to inhibit their activity. Because several neurotransmitters act through Gα_o to inhibit HSN function, it appears that loss of any one receptor, such as EGL-47, causes only mild defects. Gα_o apparently integrates signaling from multiple receptors in the HSNs, including EGL-47, to set the frequency of egg-laying behavior.