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The Journal of Neuroscience, September 29, 2004, 24(39):8522-8530; doi:10.1523/JNEUROSCI.1915-04.2004

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Cellular/Molecular
Activation of EGL-47, a G{alpha}o-Coupled Receptor, Inhibits Function of Hermaphrodite-Specific Motor Neurons to Regulate Caenorhabditis elegans Egg-Laying Behavior

James J. Moresco1 and Michael R. Koelle2

Departments of 1Genetics and 2Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520

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

Key words: EGL-47; egg-laying behavior; Caenorhabditis elegans; G-protein-coupled receptor; G{alpha}o; HSN neuron


Received Feb 6, 2004; revised July 13, 2004; accepted July 30, 2004.




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