Neural modulation of Stress Response in C.elegans

DE ROSA MJ; ALKEMA M; VEUTHEY T; BLANCO MG; RAYES D

Montevideo

Congreso; First Latin American Worm Meeting; 2017

Instituto Pasteur Montevideo

In response to environmentalchallenges cells can trigger widely conserved mechanisms to minimize cellulardamages. The coordination of this intrinsic capacity in multicellular organismsis crucial. Studies in C. eleganshave shown that the nervous system plays a key role in this coordination.  However, the signal that integrates stressperception with the response in non-neuronal cells is unknown. Our analysis ofthe C.elegans wiring map reveals thatthe circuits activated upon stress converge in the tyraminergic neuron, RIM. Tyramine(TA) is the invertebrate counterpart for adrenaline. We found that, even underfavorable growth conditions, TA-deficient animals exhibit universal hallmarksof stressed organisms, such as autophagy, lypolisis and Heat Shock Proteininduction. These mutants are resistant to thermal and oxidative stress, starvationand pathogens. Null mutants of tyra-3, aTA-activated GPCR receptor gene, are also resistant to stress. Despite tyra-3 is expressed in neurons andintestine, 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-dependentcoordination of stress response. Therefore, inhibition of TA release is a neuroendocrine signal that negatively modulatesinsulin pathways leading to a coordinated stress response in C.elegans. This study contributes to the understanding of the neurohormonalsignaling underlaying stress response regulation in multicellular organisms.