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

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

doi:10.7554/eLife.38636

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

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

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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 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.

Original language	English
Article number	e38636
Number of pages	9
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.38636
Publication status	Published - 27 Sept 2018

Keywords

D. melanogaster
damage-associated molecular pattern
DAMP
immunology
inflammation
innate immunity
JAK/STAT pathway
sterile inflammation
tissue injury

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Gordon, O., Henry, C. M., Srinivasan, N., Ahrens, S., Franz, A., Deddouche, S., Chakravarty, P., Phillips, D., George, R., Kjaer, S., Frith, D., Snijders, A. P., Valente, R. S., Simoes da Silva, C. J., Teixeira, L., Thompson, B., Dionne, M. S., Wood, W., & Reis E Sousa, C. (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

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

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 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.",

keywords = "D. melanogaster, damage-associated molecular pattern, DAMP, immunology, inflammation, innate immunity, JAK/STAT pathway, sterile inflammation, tissue injury",

author = "Oliver Gordon and Henry, {Conor M.} and Naren Srinivasan and Susan Ahrens and Anna Franz and Safia Deddouche and Probir Chakravarty and David Phillips and Roger George and Svend Kjaer and David Frith and Snijders, {Ambrosius P.} and Valente, {Rita S.} and {Simoes da Silva}, {Carolina J.} and Luis Teixeira and Barry Thompson and Dionne, {Marc S.} and Will Wood and {Reis E Sousa}, Caetano",

year = "2018",

month = sep,

day = "27",

doi = "10.7554/eLife.38636",

language = "English",

volume = "7",

journal = "eLife",

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Gordon, O, Henry, CM, Srinivasan, N, Ahrens, S, Franz, A, Deddouche, S, Chakravarty, P, Phillips, D, George, R, Kjaer, S, Frith, D, Snijders, AP, Valente, RS, Simoes da Silva, CJ, Teixeira, L, Thompson, B, Dionne, MS, Wood, W & Reis E Sousa, C 2018, 'α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster', eLife, vol. 7, e38636. https://doi.org/10.7554/eLife.38636

TY - JOUR

T1 - α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster

AU - Gordon, Oliver

AU - Henry, Conor M.

AU - Srinivasan, Naren

AU - Ahrens, Susan

AU - Franz, Anna

AU - Deddouche, Safia

AU - Chakravarty, Probir

AU - Phillips, David

AU - George, Roger

AU - Kjaer, Svend

AU - Frith, David

AU - Snijders, Ambrosius P.

AU - Valente, Rita S.

AU - Simoes da Silva, Carolina J.

AU - Teixeira, Luis

AU - Thompson, Barry

AU - Dionne, Marc S.

AU - Wood, Will

AU - Reis E Sousa, Caetano

PY - 2018/9/27

Y1 - 2018/9/27

N2 - 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.

AB - 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.

KW - D. melanogaster

KW - damage-associated molecular pattern

KW - DAMP

KW - immunology

KW - inflammation

KW - innate immunity

KW - JAK/STAT pathway

KW - sterile inflammation

KW - tissue injury

UR - http://www.scopus.com/inward/record.url?scp=85054368036&partnerID=8YFLogxK

U2 - 10.7554/eLife.38636

DO - 10.7554/eLife.38636

M3 - Article (Academic Journal)

C2 - 30260317

AN - SCOPUS:85054368036

SN - 2050-084X

VL - 7

JO - eLife

JF - eLife

M1 - e38636

ER -

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

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