Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila.
Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila.
复制标题
Verloren负向调控果蝇IMD通路依赖的抗菌肽的表达。
DOI：
10.1038/s41598-021-94973-0
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发表时间：
2021-07-30
影响因子：
4.6
通讯作者：
Goto A
中科院分区：
文献类型：
--
作者：
Prakash P;Roychowdhury-Sinha A;Goto A
果蝇免疫缺陷（IMD）信号通路与人类肿瘤坏死因子受体（TNFR）信号通路相似，并且优先被革兰氏阴性菌感染激活。最近的研究强调了IMD通路调节的重要性，因为它在多个水平上受到许多负调节因子的严格控制。在这里，我们报告了一种新的IMD途径的负调节剂，Verloren（Velo）。Velo沉默导致IMD途径依赖性抗菌肽（AMP）的组成型表达，大肠杆菌刺激进一步增强AMP表达。上位性分析表明，Velo敲低介导的AMP上调依赖于IMD途径的典型成员。使用过表达构建体的免疫荧光研究显示Velo存在于细胞核和细胞质中，但大部分（~ 75%）位于细胞核中。我们还从体内分析中观察到，Velo敲除果蝇表现出AMP表达的显著上调和细菌负荷的降低。存活实验表明，Velo基因敲除果蝇寿命短，易受致病性革兰氏阴性菌铜绿假单胞菌感染。综上所述，这些数据表明Velo是IMD途径的另外一种新的负调节剂，可能在细胞核和细胞质中起作用。
Drosophila immune deficiency (IMD) pathway is similar to the human tumor necrosis factor receptor (TNFR) signaling pathway and is preferentially activated by Gram-negative bacterial infection. Recent studies highlighted the importance of IMD pathway regulation as it is tightly controlled by numbers of negative regulators at multiple levels. Here, we report a new negative regulator of the IMD pathway, Verloren (Velo). Silencing of Velo led to constitutive expression of the IMD pathway dependent antimicrobial peptides (AMPs), and Escherichia coli stimulation further enhanced the AMP expression. Epistatic analysis indicated that Velo knock-down mediated AMP upregulation is dependent on the canonical members of the IMD pathway. The immune fluorescent study using overexpression constructs revealed that Velo resides both in the nucleus and cytoplasm, but the majority (~ 75%) is localized in the nucleus. We also observed from in vivo analysis that Velo knock-down flies exhibit significant upregulation of the AMP expression and reduced bacterial load. Survival experiments showed that Velo knock-down flies have a short lifespan and are susceptible to the infection of pathogenic Gram-negative bacteria, P. aeruginosa. Taken together, these data suggest that Velo is an additional new negative regulator of the IMD pathway, possibly acting in both the nucleus and cytoplasm.
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影响因子：
4.5
作者：
Fernando MD;Kounatidis I;Ligoxygakis P
通讯作者：
Ligoxygakis P
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
6.7
作者：
Bischoff V;Vignal C;Duvic B;Boneca IG;Hoffmann JA;Royet J
通讯作者：
Royet J
DOI：
10.15252/embj.201488456
发表时间：
2014-10-16
期刊：
The EMBO journal
影响因子：
--
作者：
Bonnay F;Nguyen XH;Cohen-Berros E;Troxler L;Batsche E;Camonis J;Takeuchi O;Reichhart JM;Matt N
通讯作者：
Matt N
影响因子：
5.3
作者：
Costechareyre, Denis;Capo, Florence;Royet, Julien
通讯作者：
Royet, Julien