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

Abstract

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 cell-to-cell signaling, as biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in the nematode 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 the sensing of osas#9. The TYRA-2/osas#9 signaling system represents an inter-organismal communication channel that evolved via co-option of a neurotransmitter and its cognate receptor.

Plasticity of pheromone-mediated avoidance behavior in C. elegans

“…As a dauer-inducing cue, ascaroside pheromones act as a population density indicator to regulate growth in the early larval developmental stage: high pheromone concentrations cause animals to enter into an alternative non-aging, stressresistant, and developmentally arrested dauer larval stage (Butcher et al, 2007;Butcher et al, 2009;Golden & Riddle, 1982, 1984Jeong et al, 2005;Pungaliya et al, 2009;Srinivasan et al, 2008) (Table 1). Subsequently, over a dozen research groups have shown that ascaroside pheromones play additional roles in several behaviors, including genderspecific attraction and repulsion, aggregation, and foraging (Artyukhin et al, 2013;Chute et al, 2019;Fagan et al, 2018;Greene, Dobosiewicz, Butcher, McGrath, & Bargmann, 1. Jeong et al, 2005;2.…”

“…In addition to ascr#3, osas#9 ascaroside was characterized as a single pheromone component which causes avoidance behavior in wild-type hermaphrodites (Artyukhin et al, 2013;Chute et al, 2019). osas#9 is an interesting ascaroside since its side chain is derived from the neurotransmitter octopamine and it is produced mainly by starved young L1 larvae (Artyukhin et al, 2013).…”

“…osas#9 is an interesting ascaroside since its side chain is derived from the neurotransmitter octopamine and it is produced mainly by starved young L1 larvae (Artyukhin et al, 2013). Chute et al found that starved but not well-fed, young adult hermaphrodites avoided micro-molar concentrations of osas#9 (Chute et al, 2019). This osas#9 avoidance was mediated by not the ADL neurons but the nociceptive ASH neurons via the osas#9-sensing tyra-2 tyramine/octopamine G proteincoupled receptor (GPCR) (Chute et al, 2019).…”

“…Chute et al found that starved but not well-fed, young adult hermaphrodites avoided micro-molar concentrations of osas#9 (Chute et al, 2019). This osas#9 avoidance was mediated by not the ADL neurons but the nociceptive ASH neurons via the osas#9-sensing tyra-2 tyramine/octopamine G proteincoupled receptor (GPCR) (Chute et al, 2019). Interestingly, the group found that trya-2 expression was increased in starved worms, suggesting that changes in the expression level of the osas#9-chemoreceptor gene depending on the feeding state are responsible for starvation-dependent osas#9 avoidance.…”

Modulation of sensory behavior and food choice by an enteric bacteria-produced neurotransmitter

“…We also observed an effect on octanol modulation in tyra2 TA receptor mutants, primarily due to decreased octanol avoidance upon growth on OP50 (4.3 ± 0.25s for tyra2 vs. 2.9 ± 0.13s for WT). TYRA-2 has recently been shown to mediate responses to an OA-linked pheromone 36 , although the reason for the observed effect in OP50-grown animals is currently unclear. Expression of octr1 cDNA in the ASH/ASI sensory neurons restored octanol modulation (Fig.…”