Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases.
Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases.
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DOI：
10.1371/journal.ppat.0010024
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发表时间：
2005-11
期刊：
影响因子：
6.7
通讯作者：
Howard JC
中科院分区：
文献类型：
--
作者：
Martens S;Parvanova I;Zerrahn J;Griffiths G;Schell G;Reichmann G;Howard JC
p47 GTPases是γ-干扰素诱导的抗弓形虫细胞自主免疫所必需的，但其机制尚不清楚。我们发现p47 GTP酶，包括IIGP 1，在含有T.刚地。积累是GTP依赖性的，需要活的寄生虫。IIGP 1的聚集经历了一个成熟的过程，伴随着寄生虫液泡膜的泡状化。这一过程的高潮是寄生虫液泡的破坏，最后是寄生虫本身的破坏。IIGP 1的过表达导致加速的空泡破坏，而IIGP 1的显性阴性形式干扰素-γ介导的细胞内寄生虫的杀伤。IIGP 1基因的靶向缺失导致IFN-γ介导的T.小鼠星形胶质细胞中的弓形虫生长限制。 刚地弓形虫是一种小型单细胞寄生虫，几乎感染包括人类在内的所有温血动物。感染后，T.弓形虫并不停留在细胞外液如血液中，而是主动侵入体细胞。寄生虫已经发展出复杂的机制，使其能够在其入侵的细胞内形成所谓的寄生虫空泡（PV）。在这个空泡内，寄生虫繁殖，直到宿主细胞破裂，后代被释放到细胞外空间，感染更多的细胞。宿主细胞已经发展出几种特殊的机制来对抗寄生虫。在小鼠中，这些机制包括一个蛋白质家族，p47 GTP酶，它是由称为干扰素的免疫警报因子诱导的。本研究旨在探讨小鼠p47 GTP酶的功能。该研究表明，p47 GTP酶在感染后不久在PV上组装，显然形成“膜攻击复合物”。在一小时内，PV膜显示出损坏的迹象，膨胀成小的外折叠，以小泡的形式与膜分离。不久之后，PV膜破裂，寄生虫恶化。p47 GTPases与发动蛋白GTPases有几个共同的特性，使细胞膜变形，这表明p47 GTPases以类似的机制方式发挥作用。
The p47 GTPases are essential for interferon-γ-induced cell-autonomous immunity against the protozoan parasite, Toxoplasma gondii, in mice, but the mechanism of resistance is poorly understood. We show that the p47 GTPases, including IIGP1, accumulate at vacuoles containing T. gondii. The accumulation is GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a maturation-like process accompanied by vesiculation of the parasitophorous vacuole membrane. This culminates in disruption of the parasitophorous vacuole and finally of the parasite itself. Over-expression of IIGP1 leads to accelerated vacuolar disruption whereas a dominant negative form of IIGP1 interferes with interferon-γ-mediated killing of intracellular parasites. Targeted deletion of the IIGP1 gene results in partial loss of the IFN-γ-mediated T. gondii growth restriction in mouse astrocytes. Toxoplasma gondii is a small unicellular parasite infecting virtually every warm-blooded animal including humans. After infection, T. gondii does not stay in extracellular fluids such as the blood, but actively invades body cells. The parasite has developed elaborate mechanisms enabling it to form a so-called parasitophorous vacuole (PV) within the cell it invades. Within this vacuole the parasite multiplies until the host cell ruptures and the progeny are released into the extracellular space to infect further cells. Host cells have developed several special mechanisms to combat the parasite. In mice, these mechanisms include a protein family, the p47 GTPases, which are induced by immune-alert factors called interferons. This study begins to address how the mouse p47 GTPases function. The study shows that the p47 GTPases assemble on the PV very shortly after infection, apparently to form a “membrane attack complex.” Within an hour the PV membrane shows signs of damage, bulging into small out-foldings that separate from the membrane in small vesicles. Shortly afterward the PV membrane ruptures and the parasite deteriorates. The p47 GTPase have several properties in common with the dynamin GTPases, which deform cellular membranes, suggesting that the p47 GTPases function in a mechanistically similar manner.
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影响因子：
5.4
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