Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole.
Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole.
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DOI：
10.1111/j.1462-5822.2010.01443.x
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发表时间：
2010-07
影响因子：
3.4
通讯作者：
Howard JC
中科院分区：
文献类型：
--
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
免疫相关的GTP酶（IRGs）是干扰素诱导小鼠抗弓形虫的细胞内抵抗机制。IRG蛋白在寄生虫空泡膜（PVM）上积累，导致其破坏和寄生虫死亡。IRG如何瞄准PVM是未知的。我们发现，积累IRGs的PVM开始后几分钟寄生虫入侵和增加约1小时。靶向独立于几个信号通路和微管网络发生，表明IRG转运是扩散驱动的。然而，在没有自噬调节剂Atg 5的情况下，PVM上IRG积累的强度降低。在野生型细胞中，IRG蛋白以一定的顺序在PVM上协同积累，反映了时间层次，Irgb 6和Irgb 10显然是先锋。加载IRG蛋白到毒力弓形虫株的空泡上是减弱的，并且两个先驱IRG受影响最大。多态性棒状体激酶，ROP 16，ROP 18和催化失活蛋白质，ROP 5A-D，不是单独负责这种效果。因此，IRG蛋白可以保护小鼠免受弓形虫弱毒株的侵害，但对强毒株却无效。IRG蛋白在抵抗弓形虫中的复杂的合作行为可能暗示在毒力机制中也存在未发现的复杂性。
The immunity-related GTPases (IRGs) constitute an interferon-induced intracellular resistance mechanism in mice against Toxoplasma gondii. IRG proteins accumulate on the parasitophorous vacuole membrane (PVM), leading to its disruption and to death of the parasite. How IRGs target the PVM is unknown. We show that accumulation of IRGs on the PVM begins minutes after parasite invasion and increases for about 1 h. Targeting occurs independently of several signalling pathways and the microtubule network, suggesting that IRG transport is diffusion-driven. The intensity of IRG accumulation on the PVM, however, is reduced in absence of the autophagy regulator, Atg5. In wild-type cells IRG proteins accumulate cooperatively on PVMs in a definite order reflecting a temporal hierarchy, with Irgb6 and Irgb10 apparently acting as pioneers. Loading of IRG proteins onto the vacuoles of virulent Toxoplasma strains is attenuated and the two pioneer IRGs are the most affected. The polymorphic rhoptry kinases, ROP16, ROP18 and the catalytically inactive proteins, ROP5A–D, are not individually responsible for this effect. Thus IRG proteins protect mice against avirulent strains of Toxoplasma but fail against virulent strains. The complex cooperative behaviour of IRG proteins in resisting Toxoplasma may hint at undiscovered complexity also in virulence mechanisms.
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影响因子：
3.2
作者：
Bonhomme, A;Maine, GT;Pinon, JM
通讯作者：
Pinon, JM
影响因子：
3.4
作者：
El Hajj, Hiba;Lebrun, Maryse;Dubremetz, Jean Francois
通讯作者：
Dubremetz, Jean Francois
影响因子：
3.1
作者：
GROSS, U;MULLER, WA;HEESEMANN, J
通讯作者：
HEESEMANN, J
影响因子：
3.1
作者：
Halonen, SK;Taylor, GA;Weiss, LM
通讯作者：
Weiss, LM
DOI：
10.1073/pnas.0510319103
发表时间：
2006-07-05
影响因子：
11.1
作者：
Boyle, Jon P.;Rajasekar, Badri;Boothroyd, John C.
通讯作者：
Boothroyd, John C.