Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila

eLife

Marc S Dionne¹  Olaf Groß¹  Fabian Hersperger¹  Jiawen Dou¹  Crystal M Vincent²  Jessica Sharrock³  Daria E Siekhaus⁴  Attila Gyoergy⁴  Katrin Kierdorf⁴  Pinar Ustaoglu⁴ 

[1] Department of Life Sciences, Imperial College London, London, United Kingdom;Faculty of Biology, University of Freiburg, Freiburg, Germany;Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany;MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom;

关键词: muscle;    insulin/AKT;    JAK/STAT;    macrophages;    metabolism;    plasmatocytes;   

DOI  :  10.7554/eLife.51595

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown