CONICET | Buscador de Institutos y Recursos Humanos

In response to environmental challenges, such as thermal and oxidative changes or nutrient deprivation, cells can trigger widely conserved mechanisms with the aim of maintaining protein homeostasis and minimize intracellular protein aggregation. These mechanisms of stress response include the induction of heat shock protein(HSPs), to prevent protein misfolding, and the up-regulation of enzymes that protect against oxidative stress. Another process that is triggered in stressed cells is the autophagy, which permits the degradation of different biomolecules to satisfying cell energy demands and maintaining the proteostasis. The coordination of this intrinsic capacity in multicellular organisms is crucial.Studies in C. elegans showed that the nervous system plays a keyrole 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 and HSPs induction. These mutants are resistant to thermal and oxidative stress and starvation. Null mutants of tyra-3, a TA-activated adrenergic-like GPCR receptor, 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 toa coordinated stress response in C. elegans. This study contributes to the understanding of the neurohormonal signaling underlaying stress response regulation in multicellular organisms.