α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster

  1. Oliver Gordon
  2. Conor M Henry
  3. Naren Srinivasan
  4. Susan Ahrens
  5. Anna Franz
  6. Safia Deddouche
  7. Probir Chakravarty
  8. David Phillips
  9. Roger George
  10. Svend Kjaer
  11. David Frith
  12. Ambrosius P Snijders
  13. Rita S Valente
  14. Carolina J Simoes da Silva
  15. Luis Teixeira
  16. Barry Thompson
  17. Marc S Dionne
  18. Will Wood
  19. Caetano Reis e Sousa  Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. University of Bristol, United Kingdom
  3. Instituto Gulbenkian de Ciência, Portugal
  4. Imperial College London, United Kingdom
  5. University of Edinburgh, United Kingdom

Abstract

Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger or modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised by DNGR-1, an innate immune receptor. Previously we suggested that actin is also a DAMP in Drosophila melanogaster by inducing STAT-dependent (Srinivasan et al., 2016). Here, we revise that conclusion and report that α-actinin is far more potent than actin at inducing the same STAT response and can be found in trace amounts in actin preparations. Recombinant expression of actin or α-actinin in bacteria demonstrated that only α-actinin could drive the expression of STAT target genes in Drosophila. The response to injected α-actinin required the same signalling cascade that we had identified in our previous work using actin preparations. Taken together, these data indicate that α-actinin rather than actin drives STAT activation when injected into Drosophila.

Data availability

Data generated or analysed during this study are included in the manuscript. Mass spectrometry data were uploaded as supporting file.

Article and author information

Author details

  1. Oliver Gordon

    Immunobiology Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Conor M Henry

    Immunobiology Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Naren Srinivasan

    Immunobiology Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Susan Ahrens

    Immunobiology Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Anna Franz

    Department of Biochemistry, Biomedical Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Safia Deddouche

    Immunobiology Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Probir Chakravarty

    Bioinformatics and Biostatistics Facility, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. David Phillips

    Genomics-Equipment Park, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Roger George

    The Structural Biology Science Technology Platform, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Svend Kjaer

    Structural Biology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. David Frith

    Proteomics, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Ambrosius P Snijders

    Proteomics, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Rita S Valente

    Instituto Gulbenkian de Ciência, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  14. Carolina J Simoes da Silva

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Luis Teixeira

    Instituto Gulbenkian de Ciência, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8326-6645
  16. Barry Thompson

    Epithelial Biology Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0103-040X
  17. Marc S Dionne

    Department of Life Sciences, Imperial College London, London, United Kingdom
    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
  18. Will Wood

    MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  19. Caetano Reis e Sousa

    Immunobiology Laboratory, The Francis Crick Institute, London, United Kingdom
    For correspondence
    Caetano@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7392-2119

Funding

Francis Crick Institute (FC001136)

  • Caetano Reis e Sousa

Wellcome Trust (WT106973MA)

  • Caetano Reis e Sousa

Federation of European Biochemical Societies

  • Conor M Henry

Fundação para a Ciencia e Tecnologia (PTDC/BEX- GMG/3128/2014)

  • Luis Teixeira

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bruno Lemaître, Ecole Polytechnique Fédérale de Lausanne, Switzerland

Version history

  1. Received: May 25, 2018
  2. Accepted: September 26, 2018
  3. Accepted Manuscript published: September 27, 2018 (version 1)
  4. Version of Record published: October 3, 2018 (version 2)

Copyright

© 2018, Gordon 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. Oliver Gordon
  2. Conor M Henry
  3. Naren Srinivasan
  4. Susan Ahrens
  5. Anna Franz
  6. Safia Deddouche
  7. Probir Chakravarty
  8. David Phillips
  9. Roger George
  10. Svend Kjaer
  11. David Frith
  12. Ambrosius P Snijders
  13. Rita S Valente
  14. Carolina J Simoes da Silva
  15. Luis Teixeira
  16. Barry Thompson
  17. Marc S Dionne
  18. Will Wood
  19. Caetano Reis e Sousa
(2018)
α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster
eLife 7:e38636.
https://doi.org/10.7554/eLife.38636

Share this article

https://doi.org/10.7554/eLife.38636

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