Torso-like is a component of the hemolymph and regulates the insulin signalling pathway in Drosophila

In Drosophila key developmental transitions are governed by the steroid hormone ecdysone. A number of neuropeptide-activated signalling pathways control ecdysone production in response to environmental signals, including the insulin signalling pathway, which regulates ecdysone production in response to nutrition. Here, we find that the Membrane Attack Complex/Perforin-like protein Torso-like, best characterised for its role in activating the Torso receptor tyrosine kinase in early embryo patterning, also regulates the insulin signalling pathway in Drosophila. We previously reported that the small body size and developmental delay phenotypes of torso-like null mutants resemble those observed when insulin signalling is reduced. Here we report that, in addition to growth defects, torso-like mutants also display metabolic and nutritional plasticity phenotypes characteristic of mutants with impaired insulin signalling. We further find that in the absence of torso-like the expression of insulin-like peptides is increased, as is their accumulation in the insulin-producing cells. Finally, we show that Torso-like is a component of the hemolymph and that it is required in the prothoracic gland to control developmental timing and body size. Taken together, our data suggest that the secretion of Torso-like from the prothoracic gland influences the activity of insulin signalling throughout the body in Drosophila.\n\nARTICLE SUMMARYIn many animals distinct developmental transitions are crucial for the coordinated progression from the juvenile stage to adulthood. In Drosophila, the transition from an immature larva into a reproductively mature adult is controlled by the steroid hormone ecdysone. Several neuropeptide-activated signalling pathways, including the insulin signalling pathway, regulate ecdysone production in response to environmental cues. Here we find that the perforin-like protein Torso-like regulates the insulin signalling pathway. We show that Torso-like is secreted into circulation where it acts to influence insulin-like peptide activity, revealing a novel mechanism for the regulation of insulin signalling in Drosophila.