The E2-like conjugation enzyme Atg3 promotes binding of IRG and Gbp proteins to Chlamydia- and Toxoplasma-containing vacuoles and host resistance.
The E2-like conjugation enzyme Atg3 promotes binding of IRG and Gbp proteins to Chlamydia- and Toxoplasma-containing vacuoles and host resistance.
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E2样共轭酶ATG3促进了IRG和GBP蛋白与衣原体和含毒素的液泡的结合以及宿主的耐药性。
DOI：
10.1371/journal.pone.0086684
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Coers J
中科院分区：
文献类型：
--
作者：
Haldar AK;Piro AS;Pilla DM;Yamamoto M;Coers J
对细菌病原体沙眼衣原体（Chlamydia trachomatis）和原生动物病原体刚地弓形虫（Toxoplasma gondii）的细胞自主免疫由两个干扰素（IFN）诱导的GTP酶家族控制：免疫相关GTP酶（IRGs）和鸟苷酸结合蛋白（Gbps）。这两个GTdR家族的成员与含病原体的空泡（PV）相关联，并特异性地向细胞内感染部位征求抗菌素耐药途径。将IRG和Gbp蛋白正确递送至PV需要自噬因子Atg5。Atg 5是蛋白复合物的一部分，其促进泛素样蛋白Atg 8从E2样缀合酶Atg 3转移到脂质磷脂酰乙醇胺。在这里，我们表明，Atg3的表达，类似于Atg5的表达，需要IRG和Gbp蛋白对接到PV。我们进一步证明，显性活性，GTP锁定IRG蛋白变体的表达拯救PV靶向缺陷的Atg3和Atg5缺陷细胞，这表明可能的作用，Atg蛋白在IRG蛋白的激活。最后，我们表明IFN诱导的细胞自主抵抗C。小鼠细胞中的沙眼衣原体感染不仅依赖于Atg5和IRG蛋白，如前所述，还需要Atg3和Gbp蛋白的表达。这些发现为更好地理解IRG和Gbp依赖的细胞自主抗性及其由Atg蛋白调节提供了基础。
Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3- and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG- and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
6.7
作者：
Martens S;Parvanova I;Zerrahn J;Griffiths G;Schell G;Reichmann G;Howard JC
通讯作者：
Howard JC
影响因子：
3.4
作者：
Khaminets A;Hunn JP;Könen-Waisman S;Zhao YO;Preukschat D;Coers J;Boyle JP;Ong YC;Boothroyd JC;Reichmann G;Howard JC
通讯作者：
Howard JC
影响因子：
4.8
作者：
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通讯作者：
Pfeffer, Klaus
影响因子：
64.8
作者：
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通讯作者：
Mizushima, N