Toxoplasma gondii Uses unusual sorting mechanisms to deliver transmembrane proteins into the host-cell vacuole
Toxoplasma gondii Uses unusual sorting mechanisms to deliver transmembrane proteins into the host-cell vacuole
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DOI：
10.1111/j.1600-0854.2008.00793.x
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发表时间：
2008-10-01
期刊：
影响因子：
4.5
通讯作者：
Cesbron-Delauw, Marie-France
中科院分区：
文献类型：
--
作者：
Gendrin, Claire;Mercier, Corinne;Cesbron-Delauw, Marie-France
顶复门寄生虫弓形虫感染的关键步骤是形成一个膜结合区室，寄生虫在其中增殖。这一过程依赖于一组分泌细胞器，在入侵时将其内容物排放到宿主细胞中。在这些细胞器中，致密颗粒专门输出跨膜（TM）GRA蛋白，这是成熟的寄生虫液泡（PV）膜的主要成分。真核病原体如何输出和分类膜结合蛋白质，目的是宿主细胞仍然是知之甚少的机制水平。在这项研究中，我们表明，可溶性贩运的PV靶向GRA 5 TM蛋白是寄生虫特异性的：当在哺乳动物细胞中表达时，GRA 5是针对质膜和行为作为一个完整的膜蛋白与I型拓扑。我们还证明了GRA 5 N-末端胞外域的双重作用，这足以防止寄生虫内的膜整合，并且对于分选和分泌后膜插入空泡膜是必不可少的。这些结果与一般规则相反，该规则规定，包含在胞质尾区和/或TM结构域的完整膜蛋白决定其细胞定位。他们还强调了多样性的排序机制，导致专门的分泌过程，独特的适应细胞内寄生。
A critical step in infection by the apicomplexan parasite Toxoplasma gondii is the formation of a membrane-bound compartment within which the parasite proliferates. This process relies on a set of secretory organelles that discharge their contents into the host cell upon invasion. Among these organelles, the dense granules are specialized in the export of transmembrane (TM) GRA proteins, which are major components of the mature parasitophorous vacuole (PV) membrane. How eukaryotic pathogens export and sort membrane-bound proteins destined for the host cell is still poorly understood at the mechanistic level. In this study, we show that soluble trafficking of the PV-targeted GRA5 TM protein is parasite specific: when expressed in mammalian cells, GRA5 is targeted to the plasma membrane and behaves as an integral membrane protein with a type I toplogy. We also demonstrate the dual role of the GRA5 N-terminal ectodomain, which is sufficient to prevent membrane integration within the parasite and is essential for both sorting and post-secretory membrane insertion into the vacuolar membrane. These results contrast with the general rule that states that information contained within the cytoplasmic tail and/or the TM domain of integral membrane proteins dictates their cellular localization. They also highlight the diversity of sorting mechanisms that leads to the specialization of secretory processes uniquely adapted to intracellular parasitism.