Distribution of malaria parasite-derived phosphatidylcholine in the infected erythrocyte.
Distribution of malaria parasite-derived phosphatidylcholine in the infected erythrocyte.
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疟疾寄生虫以多种方式修饰宿主红细胞，导致宿主红细胞的变形性、粘附性和通透性发生变化。这些变化大多是由寄生虫输出到宿主红细胞的蛋白质介导的，在那里这些蛋白质与宿主细胞骨架相互作用，或在受感染的红细胞的质膜中形成复合体。此外，疟疾寄生虫在受感染的红细胞内诱导形成膜室--寄生液泡、管泡网络(TVN)、毛雷尔裂隙和小囊泡--而红细胞通常没有内膜。感染后，红细胞膜的组成和不对称性也会发生变化。虽然寄生虫蛋白输出机制的许多方面已经变得清晰，但这些膜间隔的形成和扩大的机制几乎完全未知。为了确定寄生虫来源的磷脂是否在这些过程中发挥作用，我们应用了一种代谢标记技术，允许用荧光团标记磷脂酰胆碱。由于宿主红细胞不能合成磷脂，在感染的红细胞内，只有寄生虫来源的磷脂酰胆碱将被用这种技术标记。结果表明，该寄生虫产生的磷脂酰胆碱分布在感染的红细胞内，包括TVN和红细胞膜，但不存在毛雷氏裂隙。有趣的是，在寄生虫入侵后不久，红细胞膜上也检测到标记的磷脂，这表明寄生虫在入侵期间可能会向宿主红细胞添加磷脂。在这里，我们描述了一种以前未被认识的疟疾寄生虫与宿主红细胞相互作用的方式，即通过将寄生虫磷脂转移到红细胞膜上。这可能会对寄生虫在宿主细胞和宿主有机体中的生存产生重要影响。我们证明了寄生虫来源的磷脂从寄生虫转移到宿主红细胞膜上，并且在寄生虫入侵细胞后产生的其他内膜至少部分是使用寄生虫来源的磷脂产生的。毛雷尔裂隙是一个例外，它是一种膜性细胞器，参与了寄生虫蛋白质到红细胞表面的运输。这表明毛雷氏裂隙是以不同于其他寄生虫诱导的膜的方式产生的。总体而言，这些发现为研究宿主-寄生虫相互作用的新方面提供了一个平台。
Malaria parasites modify their host erythrocyte in multiple ways, leading to changes in the deformability, adhesiveness, and permeability of the host erythrocyte. Most of these changes are mediated by proteins exported from the parasite to the host erythrocyte, where these proteins interact with the host cell cytoskeleton or form complexes in the plasma membrane of the infected erythrocyte. In addition, malaria parasites induce the formation of membranous compartments—the parasitophorous vacuole, the tubovesicular network (TVN), the Maurer’s clefts and small vesicles—within the infected erythrocyte, a cell that is normally devoid of internal membranes. After infection, changes also occur in the composition and asymmetry of the erythrocyte plasma membrane. Although many aspects of the mechanism of export of parasite proteins have become clear, the mechanism by which these membranous compartments are formed and expanded is almost entirely unknown. To determine whether parasite-derived phospholipids play a part in these processes, we applied a metabolic labeling technique that allows phosphatidylcholine to be labeled with a fluorophore. As the host erythrocyte cannot synthesize phospholipids, within infected erythrocytes, only parasite-derived phosphatidylcholine will be labeled with this technique. The results revealed that phosphatidylcholine produced by the parasite is distributed throughout the infected erythrocyte, including the TVN and the erythrocyte plasma membrane, but not Maurer’s clefts. Interestingly, labeled phospholipids were also detected in the erythrocyte plasma membrane very soon after invasion of the parasites, indicating that the parasite may add phospholipids to the host erythrocyte during invasion. Here, we describe a previously unappreciated way in which the malaria parasite interacts with the host erythrocyte, namely, by the transfer of parasite phospholipids to the erythrocyte plasma membrane. This likely has important consequences for the survival of the parasite in the host cell and the host organism. We show that parasite-derived phospholipids are transferred from the parasite to the host erythrocyte plasma membrane and that other internal membranes that are produced after the parasite has invaded the cell are produced, at least in part, using parasite-derived phospholipids. The one exception to this is the Maurer’s cleft, a membranous organelle that is involved in the transport of parasite proteins to the surface of the erythrocyte. This reveals that the Maurer’s cleft is produced in a different manner than the other parasite-induced membranes. Overall, these findings provide a platform for the study of a new aspect of the host-parasite interaction.
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影响因子：
6.7
作者：
Collins CR;Hackett F;Strath M;Penzo M;Withers-Martinez C;Baker DA;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
1.5
作者：
Dechamps, Sandrine;Wengelnik, Kai;Gannoun-Zaki, Laila
通讯作者：
Gannoun-Zaki, Laila
影响因子：
16.6
作者：
Baker DA;Stewart LB;Large JM;Bowyer PW;Ansell KH;Jiménez-Díaz MB;El Bakkouri M;Birchall K;Dechering KJ;Bouloc NS;Coombs PJ;Whalley D;Harding DJ;Smiljanic-Hurley E;Wheldon MC;Walker EM;Dessens JT;Lafuente MJ;Sanz LM;Gamo FJ;Ferrer SB;Hui R;Bousema T;Angulo-Barturén I;Merritt AT;Croft SL;Gutteridge WE;Kettleborough CA;Osborne SA
通讯作者：
Osborne SA
影响因子：
64.5
作者：
Maier AG;Rug M;O'Neill MT;Brown M;Chakravorty S;Szestak T;Chesson J;Wu Y;Hughes K;Coppel RL;Newbold C;Beeson JG;Craig A;Crabb BS;Cowman AF
通讯作者：
Cowman AF
影响因子：
6.7
作者：
Fraser M;Jing W;Bröer S;Kurth F;Sander LE;Matuschewski K;Maier AG
通讯作者：
Maier AG