Screening of insuline like peptides (ILPs) involved in the neural coordination of stress response in c.elegans

Abstract

The ability of organisms to appropriately respond to physiological and environmental challenges requires conserved mechanisms, known as the “stress response”. The nervous system plays a key role in the coordination of systemic stress response. Recently, we demonstrated that in basal conditions tyramine released from the RIM neuron inhibits stress response in worms. Moreover, we demonstrated that expression of the GPCR TYRA-3 in the intestine is essential for this inhibition. When exposed to a stressor, such as heat, oxidative stress or lack of nutrients, tyramine signalling from the RIM should be stop to allow the animal to respond to these stressful conditions. We also observed that the insulin receptor DAF-2 is involved in this neural regulation of stress response, suggesting the compromise of insulin/insulin-like growth factor signaling (IIS) pathway. However, which are the signals that connect the intestine, where tyra-3 is expressed, with DAF-2 in several other cells are completely unknown. With this aim, we analyzed expression pattern of some of the 40 insulin like-peptides (ILPs) of C. elegans. We found that INS-3 and INS-7 co-localize with TYRA-3 in intestine. Moreover, expression of ins-7 in RIM neuron has been previously described. We also observed that null mutants of these ILPs are as resistant to thermal and oxidative stress as tdc-1 (incapable of sinthetizing tyramine) and tyra3 null mutants. We generated double null mutants of tdc-1 and tyra-3 with ins-3 and -7 in order to study epistatic relationships. Moreover, we are analizing the effects of exogenous tyramine on ins-3 and -7 expression. This study will contribute to understand molecular mechanisms involved in neuronal regulation of stress response in a multicellular organism.