Nonredundant function of two highly homologous octopamine receptors in food-deprivation-mediated signaling in Caenorhabditis elegans.

It is common for neurotransmitters to possess multiple receptors that couple to the same intracellular signaling molecules. This study analyzes two highly homologous G-protein-coupled octopamine receptors using the model animal Caenorhabditis elegans. In C. elegans, the amine neurotransmitter octopamine induces activation of cAMP response element-binding protein (CREB) in the cholinergic SIA neurons in the absence of food through activation of the Gq-coupled octopamine receptor SER-3 in these neurons. We also analyzed another Gq-coupled octopamine receptor, SER-6, that is highly homologous to SER-3. As seen in ser-3 deletion mutants, octopamine- and food-deprivation-mediated CREB activation was decreased in ser-6 deletion mutants compared with wild-type animals, suggesting that both SER-3 and SER-6 are required for signal transduction. Cell-specific expression of SER-6 in the SIA neurons was sufficient to restore CREB activation in the ser-6 mutants, indicating that SER-6, like SER-3, functions in these neurons. Taken together, these results demonstrate that two similar G-protein-coupled receptors, SER-3 and SER-6, function in the same cells in a nonredundant manner.