The neurohormone tyramine modulates the intestinal release of insulin like-peptides (ILPs) to coordinate systemic stress response in C.elegans.

GIUNTI SEBASTIÁN; VEUTHEY T; DE ROSA MJ; RAYES D

Mar del Plata

Congreso; XXXII CONGRESO ANUAL SAN 2017; 2017

Sociedad Argentina de Investigación en Neurociencias (SAN)

The nervous system plays a pivotal role in the coordination of systemic stress response. Ourresults demonstrated that in C.elegans the neuronal release of tyramine (TA) (theinvertebrate counterpart of adrenaline) inhibits the systemic response to long-term stressors.We found that the intestinal adrenergic-like receptor TYRA-3 is involved in the tyraminergiccontrol of stress response. We also observed that the insulin receptor DAF-2 is essential forthis response, suggesting the compromise of the conserved insulin/insulin-like growth factorsignaling (IIS) pathway. However, the identity of the signals that connect these pathwaysremains unknown. Our screening of the 40 insulin like-peptides (ILPs) revealed that nullmutants of INS-3 and INS-7 are as resistant to thermal and oxidative stress as tdc-1 (incapableof synthetizing TA) and tyra-3 null mutants. We also found that INS-3 and INS-7 co-localizewith TYRA-3 in intestine. Moreover, INS-3 is down-regulated upon oxidative and thermalstress. The analysis of double null mutants (tdc-1 or tyra-3 with ins-3 and/or -7) suggest thatthese genes acts in the same pathway to modulate stress response. Therefore, we proposethat TA inhibits the systemic stress response by allowing the release of INS-3 and INS-7, whichin turn activate DAF-2 in different worm cells. This study will contribute to understandmolecular mechanisms involved in neuronal regulation of stress response in a multicellularorganism.