A neuroendocrine pathway modulating osmotic stress in Drosophila
AbstractEnvironmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. Although much progress has been made on the mechanisms and neuropeptides influencing nutritional stress, relatively little is known about the factors and pathways regulating osmotic and ionic stresses. Here, we uncover the neuropeptide Corazonin (Crz) as a neuroendocrine factor that modulates the release of an osmoregulatory peptide, CAPA, to regulate tolerance to osmotic and ionic stress. Both knockdown of Crz and acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Comprehensive mapping of the Crz receptor (CrzR) expression identified three pairs of Capa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We further show that Crz is released during dry starvation (desiccation) and acts to restore homeostasis by inhibiting CAPA release via inhibition of cAMP production in Va neurons. Finally, knockdown of CrzR in Va neurons also affects CAPA release, and consequently influences desiccation tolerance and chill-coma recovery, considered proxies for diuretic state. Thus, Crz modulates Va neurons to maintain osmotic and ionic homeostasis, which in turn influences stress tolerance. Taken together with our previous work showing that systemic Crz signaling acts to restore nutrients levels by promoting food search and feeding, we propose that Crz signaling also ensures osmotic homeostasis by inhibiting the anti-diuretic CAPA peptides. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body in Drosophila.Author summaryInsects are among the largest groups of animals and have adapted to inhabit almost all environments on Earth. Their success in surviving extreme conditions stems largely from their ability to withstand environmental stress, such as desiccation and cold. However, the neural mechanisms that are responsible for coordinating responses to counter these stresses are largely unknown. To address this, we delineate a neuroendocrine axis utilizing the neuropeptides Corazonin (Crz) and CAPA, that coordinate responses to metabolic and osmotic stress. We show that Crz modulates the release of an anti-diuretic peptide, CAPA from a set of neurosecretory cells. CAPA in turn influences osmotic and ionic balance via actions on the Malpighian tubules (the insect analogs of the kidney) and the intestine. Taken together with earlier work, our data suggest that Crz acts to restore metabolic homeostasis at starvation and as a cosenquence of energy mobilization and ensuing metabolic water production, fluid balance needs to be adjusted and therefore CAPA release is inhibited. Hence, this work provides a mechanistic understanding of the neuroendocrine mitigation of metabolic and osmotic stress by two peptide systems.