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

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 ac...

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Main Authors:	Oliver Gordon, Conor M Henry, Naren Srinivasan, Susan Ahrens, Anna Franz, Safia Deddouche, Probir Chakravarty, David Phillips, Roger George, Svend Kjaer, David Frith, Ambrosius P Snijders, Rita S Valente, Carolina J Simoes da Silva, Luis Teixeira, Barry Thompson, Marc S Dionne, Will Wood, Caetano Reis e Sousa
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2018-09-01
Series:	eLife
Subjects:	innate immunity damage-associated molecular pattern tissue injury JAK/STAT pathway DAMP sterile inflammation
Online Access:	https://elifesciences.org/articles/38636

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record_format	Article
spelling	doaj-ee564ecab5b84fc6bb5c81c5b3bb58ec2021-05-05T16:10:37ZengeLife Sciences Publications LtdeLife2050-084X2018-09-01710.7554/eLife.38636α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogasterOliver Gordon0https://orcid.org/0000-0002-2567-2482Conor M Henry1https://orcid.org/0000-0001-7504-5121Naren Srinivasan2Susan Ahrens3Anna Franz4Safia Deddouche5Probir Chakravarty6David Phillips7Roger George8Svend Kjaer9David Frith10Ambrosius P Snijders11Rita S Valente12Carolina J Simoes da Silva13Luis Teixeira14https://orcid.org/0000-0001-8326-6645Barry Thompson15https://orcid.org/0000-0002-0103-040XMarc S Dionne16https://orcid.org/0000-0002-8283-1750Will Wood17Caetano Reis e Sousa18https://orcid.org/0000-0001-7392-2119Immunobiology Laboratory, The Francis Crick Institute, London, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomDepartment of Biochemistry, Biomedical Sciences, University of Bristol, Bristol, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomBioinformatics, The Francis Crick Institute, London, United KingdomGenomics-Equipment Park, The Francis Crick Institute, London, United KingdomStructural Biology, The Francis Crick Institute, London, United KingdomStructural Biology, The Francis Crick Institute, London, United KingdomProteomics, The Francis Crick Institute, London, United KingdomProteomics, The Francis Crick Institute, London, United KingdomInstituto Gulbenkian de Ciencia, Oeiras, PortugalDepartment of Life Sciences, Imperial College London, London, United KingdomInstituto Gulbenkian de Ciencia, Oeiras, PortugalEpithelial Biology Laboratory, The Francis Crick Institute, London, United KingdomMRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United KingdomEdinburgh Medical School, MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomDamage-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 genes (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.https://elifesciences.org/articles/38636innate immunitydamage-associated molecular patterntissue injuryJAK/STAT pathwayDAMPsterile inflammation
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Oliver Gordon Conor M Henry Naren Srinivasan Susan Ahrens Anna Franz Safia Deddouche Probir Chakravarty David Phillips Roger George Svend Kjaer David Frith Ambrosius P Snijders Rita S Valente Carolina J Simoes da Silva Luis Teixeira Barry Thompson Marc S Dionne Will Wood Caetano Reis e Sousa
spellingShingle	Oliver Gordon Conor M Henry Naren Srinivasan Susan Ahrens Anna Franz Safia Deddouche Probir Chakravarty David Phillips Roger George Svend Kjaer David Frith Ambrosius P Snijders Rita S Valente Carolina J Simoes da Silva Luis Teixeira Barry Thompson Marc S Dionne Will Wood Caetano Reis e Sousa α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster eLife innate immunity damage-associated molecular pattern tissue injury JAK/STAT pathway DAMP sterile inflammation
author_facet	Oliver Gordon Conor M Henry Naren Srinivasan Susan Ahrens Anna Franz Safia Deddouche Probir Chakravarty David Phillips Roger George Svend Kjaer David Frith Ambrosius P Snijders Rita S Valente Carolina J Simoes da Silva Luis Teixeira Barry Thompson Marc S Dionne Will Wood Caetano Reis e Sousa
author_sort	Oliver Gordon
title	α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster
title_short	α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster
title_full	α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster
title_fullStr	α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster
title_full_unstemmed	α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster
title_sort	α-actinin accounts for the bioactivity of actin preparations in inducing stat target genes in drosophila melanogaster
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2018-09-01
description	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 genes (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.
topic	innate immunity damage-associated molecular pattern tissue injury JAK/STAT pathway DAMP sterile inflammation
url	https://elifesciences.org/articles/38636
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α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster

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