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

α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster.
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DOI:
10.7554/elife.38636
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发表时间:
2018-09-27
期刊:
影响因子:
7.7
通讯作者:
Reis e Sousa C
Reis e Sousa C
中科院分区:
生物学1区
文献类型:
--
作者:
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

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损伤相关分子模式(DAMP)是由死亡细胞暴露或释放的分子,触发或调节免疫和组织修复。在脊椎动物中,细胞骨架成分F-肌动蛋白是一种由DNGR-1(一种天然免疫受体)特异性识别的湿气。以前,我们认为肌动蛋白也是果蝇体内的一种湿气,它通过诱导依赖于STAT的基因来实现。在这里,我们修正了这一结论,并报告说,α-肌动蛋白在诱导相同的STAT反应方面远比肌动蛋白更有效,并且可以在肌动蛋白制剂中的微量中发现。肌动蛋白或α-肌动蛋白在细菌中的重组表达表明,只有α-肌动蛋白才能驱动果蝇STAT靶基因的表达。对注射的α-肌动蛋白的反应需要我们在使用肌动蛋白制剂的先前工作中确定的相同的信号级联。综上所述,这些数据表明,当注射到果蝇体内时,α-肌动蛋白而不是肌动蛋白驱动STAT激活。
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. 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.