Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila
- University of Freiburg, Germany
- Imperial College London, United Kingdom
- Institute of Science and Technology Austria, Austria
Abstract
Unpaired ligands are secreted signals that act via a GP130-like receptor, domeless, to activate JAK/STAT signaling 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 signaling as a metabolic regulator in healthy adult Drosophila muscle. Adult muscles show basal JAK-STAT signaling 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.
Data availability
Data has been made available on Zenodo, under the doi 10.5281/zenodo.3608626.
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Raw data for Kierdorf et al,Zenodo, doi:10.5281/zenodo.3608626.
Article and author information
Author details
Funding
Wellcome (Investigator Award 207467/Z/17/Z)
- Marc S Dionne
Biotechnology and Biological Sciences Research Council (Research Grant BB/P000592/1)
- Katrin Kierdorf
- Pinar Ustaoglu
- Marc S Dionne
Biotechnology and Biological Sciences Research Council (Research Grant BB/L020122/2)
- Jessica Sharrock
- Marc S Dionne
Medical Research Council (Research Grant MR/L018802/2)
- Katrin Kierdorf
- Marc S Dionne
Deutsche Forschungsgemeinschaft (Research fellowship KI-1876/1)
- Katrin Kierdorf
Biotechnology and Biological Sciences Research Council (PhD studentship BB/L502169/1)
- Jessica Sharrock
Deutsche Forschungsgemeinschaft (CIBSS-EXC-2189-Project ID 390939984)
- Fabian Hersperger
European Commission (ERC starting grant 337689)
- Olaf Gross
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
Version history
- Received: September 4, 2019
- Accepted: January 10, 2020
- Accepted Manuscript published: January 16, 2020 (version 1)
- Accepted Manuscript updated: January 20, 2020 (version 2)
- Version of Record published: February 3, 2020 (version 3)
Copyright
© 2020, Kierdorf et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila
eLife 9:e51595.
https://doi.org/10.7554/eLife.51595
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