Release of malaria circumsporozoite protein into the host cell cytoplasm and interaction with ribosomes
Release of malaria circumsporozoite protein into the host cell cytoplasm and interaction with ribosomes
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DOI：
10.1016/0166-6851(96)02701-6
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发表时间：
1996-10-30
影响因子：
1.5
通讯作者：
Frevert, U
中科院分区：
文献类型：
--
作者：
Hugel, FU;Pradel, G;Frevert, U
迄今为止，环子孢子（CS）蛋白已经涉及将疟疾子孢子引导至肝脏[Cerami等人，Cell 70，1992，1021 - 1033]。在这里，我们表明，入侵后不久，伯氏疟原虫和约氏疟原虫子孢子躺在入侵细胞中的自由和释放大量的CS蛋白到细胞质中。CS蛋白质的胞质内沉积开始于子孢子附着于宿主细胞表面期间，并在入侵后的第一个4 - 6小时期间达到高峰。最初，CS蛋白遍布感染细胞的整个细胞质，在那里它与胞质以及内质网相关的核糖体相互作用。在寄生虫随后发育为红细胞外形式期间，CS蛋白结合逐渐限于内衬宿主细胞核膜外膜的核糖体。寄生虫释放的CS蛋白在宿主细胞质中的分布模式与宿主细胞对寄生虫发展为红细胞外形式的容许性无关。它既不需要宿主细胞代谢，也不涉及内吞机制。显微注射和免疫电镜显示重组恶性疟原虫CS蛋白与内质网相关核糖体上的RNA酶敏感位点相互作用。CS蛋白与宿主细胞核糖体的普遍相互作用表明，CS蛋白在疟原虫生命周期的肝期具有细胞内功能，也可以解释啮齿动物疟疾感染过程中CD8（+）T细胞应答的产生。
To date, the circumsporozoite (CS) protein has been implicated in guiding malaria sporozoites to the liver [Cerami et al., Cell 70, 1992, 1021-1033]. Here we show that shortly after invasion, P, berghei and P. yoelii sporozoites lie free in the invaded cell and release considerable amounts of CS protein into the cytoplasm. The intracytoplasmic deposition of CS protein begins during the attachment of the sporozoite to the host cell surface and reaches its peak during the first 4-6 h after invasion. Initially, the CS protein spreads over the entire cytoplasm of the infected cell where it interacts with cytosolic as well as endoplasmic reticulum-associated ribosomes. During the subsequent development of the parasites to exoerythrocytic forms, the CS protein binding becomes gradually restricted to ribosomes lining the outer membrane of the nuclear envelope of the host cell. The distribution pattern of the parasite-released CS protein in the host cell cytoplasm is independent of the permissiveness of the host cell for the development of the parasites to exoerythrocytic forms. It requires neither the host cell metabolism nor does it involve the endocytotic machinery. Recombinant P. falciparum CS protein interacts with RNAse-sensitive sites on endoplasmic reticulum-associated ribosomes as shown by microinjection and immunoelectron microscopy. The generalized interaction of the CS protein with host cell ribosomes suggests that the CS protein has an intracellular function during the hepatic phase in the life cycle of Plasmodium and may also explain the generation of a CD8(+) T cell response in the course of rodent malaria infections.