期刊
ELIFE
卷 9, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.51595
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资金
- Wellcome [207467/Z/17/Z]
- Biotechnology and Biological Sciences Research Council [BB/P000592/1, BB/L020122/2, BB/L502169/1]
- Medical Research Council [MR/L018802/2, MR/R00997X/1]
- Deutsche Forschungsgemeinschaft [KI-1876/1, CIBSS-EXC-2189, 390939984]
- NeuroMac Graduate School [SFB/TRR167]
- European Commission ERC starting grant [337689]
- FWF [DASI_FWF01_P29638S]
- Wellcome Trust [207467/Z/17/Z] Funding Source: Wellcome Trust
- BBSRC [BB/L015129/1, BB/L020122/2, BB/P000592/1] Funding Source: UKRI
- MRC [MR/P028225/1, MR/L018802/2, MR/R00997X/1] Funding Source: UKRI
- European Research Council (ERC) [337689] Funding Source: European Research Council (ERC)
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.
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