Neuronal control of the systemic stress response in C. elegans

VEUTHEY TANIA V; GIUNTI SEBASTIAN; BLANCO MARIA GABRIELA; ALKEMA MARK; DE ROSA MARIA JOSE; RAYES DIEGO

Congreso; XXXII Congreso Anual SAN; 2017

Homeostasis is the ability of cells and organisms to maintain an internal equilibrium state. It is known that environmental factors disrupt homeostasis. In response to environmental challenges, multicellular organisms trigger conserved and tightly regulated molecular mechanisms to minimize cellular damages, known as ?stress response?. Neural coordination of systemic stress response is key to handle unfavorable conditions. The signals that coordinate sensorial stress perception with the response in non-neural cells are still unknown. We proposed to study neural modulation of stress response in C. elegans under different environmental challenges such as heat, oxidative stress or food deprivation. Our studies reveal that neural tyramine release, the invertebrate counterpart for epinephrine, leads to suppression of cellular response to these aggressions. Intestinal expression of the adrenergic-like receptor TYRA-3 is essential for this inhibition. By analyzing null mutants of insulin receptor DAF-2, we found that this neural regulation of stress response entirely depends on the highly conserved insulin/insulin-like growth factor signaling. We now aim 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 and ins-7 null mutants are also resistant to thermal and oxidative stress. Strikingly, we found that both ILPs are expressed in the tyraminergic neuron RIM, and co-express with intestinal TYRA-3. Moreover, INS-3 is down-regulated upon oxidative and thermal stress. Genetic analysis confirms that both ILPs play a key role in neural control of stress response. Our results suggest that environmental stressors, independently of their nature, leads to a common neuronal signaling to coordinate systemic stress response in C. elegans. As most of the pathways involved are conserved throughout the animal kingdom, our findings can be universally significant