DrosophilaNeuronal Glucose 6 Phosphatase is a modulator of Neuropeptide Release that regulates muscle glycogen stores via FMRFamide signaling

Abstract

SUMMARYNeuropeptides (NPs) and their cognate receptors are critical molecular effectors of diverse physiological processes and behaviors. We recently reported of a non-canonical function of theDrosophila Glucose-6-Phosphatase(G6P) gene in a subset of neurosecretory cells in the CNS that governs systemic glucose homeostasis in food deprived flies. Here, we show thatG6Pexpressing neurons define 7 groups of neuropeptide secreting cells, 5 in the brain and 2 in the thoracic ganglia. Using the glucose homeostasis phenotype as a screening tool, we show that one such group, located in the thoracic ganglia and expressing FMRFamide (FMRFaG6P) neuropeptides, is necessary and sufficient to maintain systemic glucose homeostasis in starved flies. We further show that the receptor for FMRFamides (FMRFaR) is one key target ofG6Pdependent NP signaling and essential for the build-up of glycogen stores in the jump muscle. Lastly, measurements of the Golgi apparatus ofFMRFaG6Pneurons and neuropeptide released into the hemolymph suggests thatG6Penhances FMRFa signaling by increasing the capacity of the neurosecretory system. We propose a general model in which the main role ofG6Pis to counteract glycolysis in peptidergic neurons for the purpose of optimizing the intracellular environment best suited for the expansion of the Golgi apparatus, boosting release of neuropeptides, which through the activation of specific neuropeptide receptors, enhances signaling in respective target tissues.