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Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster

Srinivasan, N; Gordon, O; Ahrens, S; Franz, A; Deddouche, S; Chakravarty, P; Phillips, D; ... Reis e Sousa, C; + view all (2016) Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster. eLife , 5 , Article e19662. 10.7554/eLife.19662. Green open access

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Abstract

Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs and adaptive immunity. Administration of actin to Drosophila melanogaster triggers a response characterised by selective induction of STAT target genes in the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor, Domeless. Notably, this response requires signalling via Shark, the Drosophila orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent on Nox activity. Thus, extracellular actin detection via a Src-family kinase-dependent cascade is an ancient means of detecting cell injury that precedes the evolution of adaptive immunity.

Type: Article
Title: Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.19662
Publisher version: http://doi.org/10.7554/eLife.19662
Language: English
Additional information: © 2016, Srinivasan et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: D. melanogaster, DAMP, JAK/STAT pathway, damage-associated molecular pattern, immunology, innate immunity, sterile inflammation, tissue injury, Actins, Alarmins, Animals, Drosophila melanogaster, Signal Transduction, Stress, Physiological
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10073340
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