PT - JOURNAL ARTICLE AU - Christopher D. Chute AU - Elizabeth M. DiLoreto AU - Ying K. Zhang AU - Diego Rayes AU - Veronica L. Coyle AU - Hee June Choi AU - Mark J. Alkema AU - Frank C. Schroeder AU - Jagan Srinivasan TI - Co-option of neurotransmitter signaling for inter-organismal communication in <em>C. elegans</em> AID - 10.1101/275693 DP - 2018 Jan 01 TA - bioRxiv PG - 275693 4099 - http://biorxiv.org/content/early/2018/09/18/275693.short 4100 - http://biorxiv.org/content/early/2018/09/18/275693.full AB - Biogenic amine neurotransmitters play a central role in metazoan biology, and both their chemical structures and cognate receptors are evolutionarily conserved. Their primary roles are in intra-organismal signaling, whereas biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in C. elegans, a neurotransmitter-sensing G protein-coupled receptor, TYRA-2, is required for avoidance responses to osas#9, an ascaroside pheromone that incorporates the neurotransmitter octopamine. Neuronal ablation, cell-specific genetic rescue, and calcium imaging show that tyra-2 expression in the nociceptive neuron ASH is necessary and sufficient to induce osas#9 avoidance. Ectopic expression in the AWA neuron, which is generally associated with attractive responses, reverses the response to osas#9, resulting in attraction instead of avoidance behavior, confirming that TYRA-2 partakes in sensing osas#9. The TYRA-2/osas#9 signaling system thus represents an inter-organismal communication channel that evolved via co-option of a neurotransmitter and its cognate receptor.