Tyramine modulates the systemic stress response by stimulating the release of intestinal insulin like-peptides (ILPs

VEUTHEY TANIA V; GIUNTI SEBASTIAN; FLORMAN JEREMY ; DE ROSA MARIA JOSE; ALKEMA MARK; RAYES DIEGO

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Congreso; 23 international C. elegans conference; 2021

The ability of multicellular organisms to respond to physiological and environmental challenges requires universally conservedmechanisms, commonly known as the ?stress response?. The nervous system plays a key role in the coordination of systemicstress response. We recently discovered that neural stress hormones released during C. elegans flight response negativelyimpact health by activating the DAF-2/IIS pathway (De Rosa, Veuthey et al, Nature, 2019). The flight response in C. elegansactivates the tyraminergic RIM neurons. Tyramine (TA) released activates an adrenergic-like GPCR (TYRA-3) in the intestine.Activation of TYRA-3, a predicted Gq-coupled receptor, leads to the stimulation of the DAF-2/IIS pathway throughout thebody of the worm. Tyramine-induced activation of the DAF-2/IIs pathway may increase the animal?s metabolic rate to satisfythe energy demands of the flight response but would inhibit the activation of cytoprotective mechanisms. Conversely, when theanimal is exposed to environmental stressors, such as heat or oxidative stress, tyramine release is inhibited, thereforepermitting the induction of cytoprotective mechanisms that include activation of transcription factors such as DAF-16/FOXOWhich are the signals that link TYRA-3 activation in the intestine with stimulation of the DAF-2/IIS pathway in other tissues?.The genome of C. elegans encodes 40 insulin-like peptides (ILPs), and 28 of them are expressed on the intestine. Recentevidence has shown that 5 of these are strong DAF-2 agonists (Zheng et al, JBC, 2018). We hypothesize that TYRA-3stimulates the release of Insulin-Like Peptides (ILPs) from the intestine that can systemically activate the DAF-2 insulin/IGF1receptor. Thus, the main aim of this work is to identify these ILPs released from the intestine during the flight response