Neuronal control of the systemic stress response in C. elegans

VEUTHEY, TANIA; GIUNTI SEBASTIÁN; BLANCO, MARÍA GABRIELA; ALKEMA M; DE ROSA MARÍA JOSÉ; RAYES D

Mar del Plata

Congreso; XXXII CONGRESO ANUAL SAN 2017; 2017

Sociedad Argentina de Investigación en Neurociencias (SAN)

Homeostasis is the ability of cells and organisms to maintain an internal equilibriumstate. It is known that environmental factors disrupt homeostasis. In response toenvironmental challenges, multicellular organisms trigger conserved and tightlyregulated molecular mechanisms to minimize cellular damages, known as ?stressresponse?. Neural coordination of systemic stress response is key to handleunfavorable conditions. The signals that coordinate sensorial stress perception withthe response in non-neural cells are still unknown. We proposed to study neuralmodulation of stress response in C. elegans under different environmental challengessuch as heat, oxidative stress or food deprivation. Our studies reveal that neuraltyramine release, the invertebrate counterpart for epinephrine, leads to suppressionof cellular response to these aggressions. Intestinal expression of the adrenergic-likereceptor TYRA-3 is essential for this inhibition. By analyzing null mutants of insulinreceptor DAF-2, we found that this neural regulation of stress response entirelydepends on the highly conserved insulin/insulin-like growth factor signaling. We nowaim to elucidate the role of the insulin like-peptides (ILPs) in this stress coordination.Our results show that, similar to worms deficient in tyraminergic signaling, ins-3 andins-7 null mutants are also resistant to thermal and oxidative stress. Strikingly, wefound that both ILPs are expressed in the tyraminergic neuron RIM, and co-expresswith intestinal TYRA- 3. Moreover, INS-3 is down-regulated upon oxidative andthermal stress. Genetic analysis confirms that both ILPs play a key role in neuralcontrol of stress response. Our results suggest that environmental stressors,independently of their nature, leads to a common neuronal signaling to coordinatesystemic stress response in C. elegans. As most of the pathways involved areconserved throughout the animal kingdom, our findings can be universally significant.