Biogenic amine neurotransmitters play a central role in metazoan nervous systems, and both their chemical structures and cognate receptors are evolutionarily highly conserved. In the nematode C. elegans, four classical neurotransmitters - serotonin, dopamine, octopamine, and tyramine - have been detected and appear to serve signaling functions related to those in insects or vertebrates (1). Interestingly, one of the small molecule pheromones released by C. elegans incorporates the monoamine octopamine. Octopamine succinylated ascaroside #9 (osas#9) is biochemically derived by connecting the neurotransmitter octopamine to an ascaroside - a universal building block of pheromones in C. elegans (2, 3). Neuronal ablation, cell-specific genetic rescue, and calcium imaging show that tyra-2, a gene coding for a G protein-coupled receptor (GPCR), expression in the nociceptive neuron ASH is both necessary and sufficient to induce avoidance of osas#9. In contrast, expression of tyra-2 in AWA, a neuron pair primarily involved in attraction, reverses the behavioral response to osas#9. These results show that TYRA-2 serves as a receptor for the neurotransmitter-derived osas#9, and thus may function in both internal signaling and sensation of external signals. The TYRA-2/osas#9 signaling system thus provides an example for the evolution of an inter-organismal communication channel via co-option of a small-molecule signal and its cognate receptor.

Co-option of neurotransmitter signaling for inter-organismal communication in C. elegans