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

  1. Katrin Kierdorf  Is a corresponding author
  2. Fabian Hersperger
  3. Jessica Sharrock
  4. Crystal M Vincent
  5. Pinar Ustaoglu
  6. Jiawen Dou
  7. Attila Gyoergy
  8. Olaf Gross
  9. Daria E Siekhaus
  10. Marc S Dionne  Is a corresponding author
  1. University of Freiburg, Germany
  2. Imperial College London, United Kingdom
  3. 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.

The following data sets were generated

Article and author information

Author details

  1. Katrin Kierdorf

    Institute of Neuropathology, University of Freiburg, Freiburg, Germany
    For correspondence
    katrin.kierdorf@uniklinik-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9272-4780
  2. Fabian Hersperger

    Institute of Neuropathology, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Jessica Sharrock

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Crystal M Vincent

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Pinar Ustaoglu

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Jiawen Dou

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Attila Gyoergy

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1819-198X
  8. Olaf Gross

    Institute of Neuropathology, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Daria E Siekhaus

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8323-8353
  10. Marc S Dionne

    Department of Life Sciences, Imperial College London, London, United Kingdom
    For correspondence
    m.dionne@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8283-1750

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

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Version history

  1. Received: September 4, 2019
  2. Accepted: January 10, 2020
  3. Accepted Manuscript published: January 16, 2020 (version 1)
  4. Accepted Manuscript updated: January 20, 2020 (version 2)
  5. 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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  1. Katrin Kierdorf
  2. Fabian Hersperger
  3. Jessica Sharrock
  4. Crystal M Vincent
  5. Pinar Ustaoglu
  6. Jiawen Dou
  7. Attila Gyoergy
  8. Olaf Gross
  9. Daria E Siekhaus
  10. Marc S Dionne
(2020)
Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila
eLife 9:e51595.
https://doi.org/10.7554/eLife.51595

Share this article

https://doi.org/10.7554/eLife.51595

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