MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom; Department of Life Sciences, Imperial College London, London, United Kingdom
Fabian Hersperger
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany
Jessica Sharrock
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom; Department of Life Sciences, Imperial College London, London, United Kingdom
Crystal M Vincent
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom; Department of Life Sciences, Imperial College London, London, United Kingdom
Pinar Ustaoglu
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom; Department of Life Sciences, Imperial College London, London, United Kingdom
Institute of Science and Technology, Klosterneuburg, Austria
Olaf Groß
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany; Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany
Unpaired ligands are secreted signals that act via a GP130-like receptor, domeless, to activate JAK/STAT signalling in Drosophila. Like many mammalian cytokines, unpaireds can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for unpaired-JAK signalling as a metabolic regulator in healthy adult Drosophila muscle. Adult muscles show basal JAK-STAT signalling activity in the absence of any immune challenge. Plasmatocytes (Drosophila macrophages) are an important source of this tonic signal. Loss of the dome receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal that must be received in muscle to control AKT activity and metabolic homeostasis.
