Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum
Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum
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DOI：
10.1073/pnas.0711067105
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发表时间：
2008-02-19
影响因子：
11.1
通讯作者：
Joiner, Keith A.
中科院分区：
文献类型：
--
作者：
Elliott, David A.;McIntosh, Michael T.;Joiner, Keith A.
在疟疾感染的血液阶段，寄生虫内化并降解宿主红细胞中的大量血红蛋白。使用连续的薄切片电子显微镜和三维重建，我们证明了四个独立的，但部分重叠，血红蛋白摄取过程可区分时间，形态学，和神经元。早期的环状阶段的寄生虫经历了一个深刻的形态转变，在这个过程中，它们像杯子一样折叠在自己身上，这样做会吞下宿主细胞的第一口细胞质。这一事件，我们称之为“大口”，似乎是独立的肌动蛋白聚合，标志着寄生虫的溶酶体区室-食物泡生物发生的第一步。第二，以前确定的吸收过程，使用cytostome，一个良好的特点和形态上不同的结构在寄生虫的表面。这个过程更类似于经典的内吞作用，产生小的（< 0.004 fI）囊泡，其由早期内体调节蛋白Rab 5a标记。第三个过程，也来自细胞口，以肌动蛋白依赖的方式产生长而细的管，以前称为细胞口管。第四条途径，我们称之为吞噬，与大吞咽类似，因为它更接近吞噬作用，除了吞噬不需要肌动蛋白聚合。这四个过程中的每一个都有疟原虫独有的方面，从而为抗疟治疗开辟了途径。
During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, which we term the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment-the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (< 0.004 fI) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.