The Molecular Identity and Sensory Signal Transduction of a Post-Mortem Necrotaxis Cue in C. elegans

Abstract

Animals sense signals from their environment to inform their behavior and decision-making. Many species have evolved to detect alarm cues released from injured or deceased conspecifics, triggering defensive responses that help them to avoid the same threats that led to the demise of other individuals in their population. Understanding the molecular nature of these signaling molecules and the methods of signal transduction provides insight into the mechanisms behind such behaviors. In Caenorhabditis elegans, the Murphy Lab identified a novel signaling molecule released from lysed worms that living conspecifics avoid. We termed this necrotaxis cue “Todstoff” (death substance). This thesis seeks to characterize the molecular identity of Todstoff, as well as its sensory signal transduction. Analysis of the Todstoff signal suggests that it is proteinaceous and smaller than 20 kDa in size, distinct from known ascaroside signals and alarm pheromones. Building upon previous work by the Murphy lab, which established that Todstoff is sensed by the ASH sensory neuron, I further elucidate the intracellular signal processing pathways involved in Todstoff detection. I demonstrate that necrotaxis requires G-protein-coupled receptor signaling, mediated by the ODR-3 G alpha subunit, as well as synaptic transmission via glutamatergic signaling. Finally, I found that C. elegans avoid lysate from other species of Caenorhabditis, but are attracted to protein precipitated from these worms, indicating that necrotaxis in response to related nematode species is likely directed by a signal separate from Todstoff. Together, the results of this thesis illustrate the existence of a novel, post-mortem inter- animal necrotaxis cue that promotes organismal longevity and survival.