Wickham M E, Rug M, Ralph S A, Klonis N, McFadden G I, Tilley L, Cowman A F
The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne 3050, Australia.
EMBO J. 2001 Oct 15;20(20):5636-49. doi: 10.1093/emboj/20.20.5636.
After invading human erythrocytes, the malarial parasite Plasmodium falciparum, initiates a remarkable process of secreting proteins into the surrounding erythrocyte cytoplasm and plasma membrane. One of these exported proteins, the knob-associated histidine-rich protein (KAHRP), is essential for microvascular sequestration, a strategy whereby infected red cells adhere via knob structures to capillary walls and thus avoid being eliminated by the spleen. This cytoadherence is an important factor in many of the deaths caused by malaria. Green fluorescent protein fusions and fluorescence recovery after photobleaching were used to follow the pathway of KAHRP deployment from the parasite endomembrane system into an intermediate depot between parasite and host, then onwards to the erythrocyte cytoplasm and eventually into knobs. Sequence elements essential to individual steps in the pathway are defined and we show that parasite-derived structures, known as Maurer's clefts, are an elaboration of the canonical secretory pathway that is transposed outside the parasite into the host cell, the first example of its kind in eukaryotic biology.
疟原虫恶性疟原虫侵入人类红细胞后,会启动一个将蛋白质分泌到周围红细胞细胞质和质膜中的显著过程。其中一种输出蛋白,即富含组氨酸的与小节相关蛋白(KAHRP),对于微血管隔离至关重要,微血管隔离是一种策略,通过该策略,受感染的红细胞通过小节结构粘附在毛细血管壁上,从而避免被脾脏清除。这种细胞粘附是许多疟疾致死病例中的一个重要因素。绿色荧光蛋白融合体和光漂白后的荧光恢复被用于追踪KAHRP从寄生虫内膜系统进入寄生虫与宿主之间的中间储存库,然后进入红细胞细胞质并最终进入小节的途径。确定了该途径中各个步骤所必需的序列元件,并且我们表明,被称为毛雷尔氏小体的寄生虫衍生结构是经典分泌途径的一种细化,该途径被转移到寄生虫外部进入宿主细胞,这是真核生物学中此类的首个例子。