"Neuronal modulation of stress response in C. elegans"

DE ROSA MJ; VEUTHEY T; BLANCO MG; ANDERSEN N; GIUNTI S; ALKEMA MJ; RAYES D

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

In response to environmentalchallenges, such as thermal and oxidative changes or nutrient deprivation, cellscan trigger widely conserved mechanisms with the aim of maintaining proteinhomeostasis and minimize intracellular protein aggregation. These mechanisms ofstress response include the induction of heat shock protein (HSPs), to preventprotein misfolding, and the up-regulation of enzymes that protect against oxidativestress. Another process that is triggered in stressed cells is the autophagy,which permits the degradation of different biomolecules to satisfying cellenergy demands and maintaining the proteostasis. The coordination ofthis intrinsic capacity in multicellular organisms is crucial.Studies in C. elegans showed that the nervoussystem plays a key role in this coordination.However, the signal that integrates stress perception with the response innon-neuronal cells is unknown. Our analysis of the C.elegans wiring map reveals that the circuits activated upon stressconverge in the tyraminergic neuron, RIM. Tyramine (TA) is the invertebratecounterpart for adrenaline. We found that, even under favorable growthconditions, TA-deficient animals exhibit universal hallmarks of stressedorganisms, such as autophagy and HSPs induction. These mutants are resistant tothermal and oxidative stress and starvation. Null mutants of tyra-3, a TA-activated adrenergic-like GPCRreceptor, are also resistant to stress. Despite tyra-3 is expressed in neurons and intestine, it is only needed inthe gut for wild-type stress resistance. Moreover, we show that the insulinreceptor DAF-2 is essential for the TA-dependent coordination of stressresponse. Therefore, inhibition of TA releaseis a neuroendocrine signal that negatively modulates insulin pathways leadingto a coordinated stress response in C. elegans. This study contributes to theunderstanding of the neurohormonal signaling underlaying stress responseregulation in multicellular organisms.