Activation of EGL-47, a Galpha(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 Galpha(o) and serves as a model for analyzing Galpha(o) signaling. Mutations that alter egg-laying frequency have identified genes encoding a number of signaling proteins that act with Galpha(o), but the receptors that activate Galpha(o) remain mostly uncharacterized. To further analyze Galpha(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 Galpha(o) specifically in the HSNs was sufficient to inhibit egg-laying behavior. Our results suggest that EGL-47 regulates egg laying by activating Galpha(o) in the HSN motor neurons to inhibit their activity. Because several neurotransmitters act through Galpha(o) to inhibit HSN function, it appears that loss of any one receptor, such as EGL-47, causes only mild defects. Galpha(o) apparently integrates signaling from multiple receptors in the HSNs, including EGL-47, to set the frequency of egg-laying behavior.