Neural modulation of stress response in C. elegans

DE ROSA MJ; ALKEMA MJ; VEUTHEY, TANIA; RAYES D; BLANCO, MARÍA GABRIELA

Buenos Aires

Congreso; 2nd Falan Congress; 2016

In response to environmental challenges cells can trigger widely conserved mechanisms to minimize cellular damages. The coordination of this intrinsic capacity in multicellular organisms is crucial. Studies in C. elegans have shown that the nervous system plays a key role in this coordination. However, the signal that integrates stress perception with the response in non-neuronal cells is unknown. Our analysis of the C.elegans wiring map reveals that the circuits activated upon stress converge in the tyraminergic neuron, RIM. Tyramine (TA) is the invertebrate counterpart for adrenaline. We found that, even under favorable growth conditions, TA-deficient animals exhibit universal hallmarks of stressed organisms, such as autophagy, lypolisis and Heat Shock Protein induction. These mutants are resistant to thermal and oxidative stress, starvation and pathogens. Null mutants of tyra-3, a TA-activated GPCR receptor gene, are also resistant to stress. Despite tyra-3 is expressed in neurons and intestine, it is only needed in the gut for wild-type stress resistance. Moreover, we show that the insulin receptor DAF-2 is essential for the TA-dependent coordination of stress response. Therefore, inhibition of TA release is a neuroendocrine signal that negatively modulates insulin pathways leading to a coordinated stress response in C.elegans. This study contributes to the understanding of the neurohormonal signaling underlaying stress response regulation in multicellular organisms.