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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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posted on 27.07.2020 by 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
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.

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