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

GIUNTI SEBASTIAN; VEUTHEY TANIA V; DE ROSA MARIA JOSE; RAYES DIEGO

Congreso; XXXII Congreso Anual SAN; 2017

The nervous system plays a pivotal role in the coordination of systemic stress response. Our results demonstrated that in C.elegans the neuronal release of tyramine (TA) (the invertebrate 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 tyraminergic control of stress response. We also observed that the insulin receptor DAF-2 is essential for this response, suggesting the compromise of the conserved insulin/insulin-like growth factor signaling (IIS) pathway. However, the identity of the signals that connect these pathways remains unknown. Our screening of the 40 insulin like-peptides (ILPs) revealed that null mutants of INS-3 and INS-7 are as resistant to thermal and oxidative stress as tdc-1 (incapable of synthetizing TA) and tyra-3 null mutants. We also found that INS-3 and INS-7 co-localize with TYRA-3 in intestine. Moreover, INS-3 is down-regulated upon oxidative and thermal stress. The analysis of double null mutants (tdc-1 or tyra-3 with ins-3 and/or -7) suggest that these genes acts in the same pathway to modulate stress response. Therefore, we propose that 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 understand molecular mechanisms involved in neuronal regulation of stress response in a multicellular organism.