TY - JOUR AB - 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. AU - Srinivasan,N AU - Gordon,O AU - Ahrens,S AU - Franz,A AU - Deddouche,S AU - Chakravarty,P AU - Phillips,D AU - Yunus,AA AU - Rosen,MK AU - Valente,RS AU - Teixeira,L AU - Thompson,B AU - Dionne,MS AU - Wood,W AU - Reis,e Sousa C DO - 10.7554/eLife.19662 PY - 2016/// SN - 2050-084X TI - Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster T2 - eLife UR - http://dx.doi.org/10.7554/eLife.19662 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000390319900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202 UR - http://hdl.handle.net/10044/1/44003 VL - 5 ER -