LISP1 is important for the egress of Plasmodium berghei parasites from liver cells
LISP1 is important for the egress of Plasmodium berghei parasites from liver cells
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DOI：
10.1111/j.1462-5822.2009.01333.x
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发表时间：
2009-09-01
影响因子：
3.4
通讯作者：
Baldacci, Patricia
中科院分区：
文献类型：
--
作者：
Ishino, Tomoko;Boisson, Bertrand;Baldacci, Patricia
大多数顶复合体是细胞内的强制性寄生虫，它们在进入宿主细胞后形成的所谓寄生液泡（PV）内繁殖。疟原虫是疟疾和对人类最致命的顶复合体的病原体，在哺乳动物宿主的肝细胞和红细胞中繁殖。尽管对于顶复合体寄生虫如何侵入PV内的宿主细胞已经有了很多了解，但对于它们如何破坏PV膜并离开宿主细胞却知之甚少。在这里，我们描述了一种被称为LISP1（肝脏特异性蛋白1）的疟原虫蛋白，它特异性地参与了寄生虫从肝细胞的排出。LISP1在寄生虫发育后期在肝细胞内表达，位于PV膜上。缺乏LISP1的细胞内寄生虫发育成肝脏分裂子，对红细胞表现出正常的感染性。然而，缺乏lisp1的肝期寄生虫不会破坏PV的膜并滞留在肝细胞内。LISP1是基因靶向研究发现的第一个参与PV膜裂解的疟原虫蛋白。
P>Most Apicomplexa are obligatory intracellular parasites that multiply inside a so-called parasitophorous vacuole (PV) formed upon parasite entry into the host cell. Plasmodium, the agent of malaria and the Apicomplexa most deadly to humans, multiplies in both hepatocytes and erythrocytes in the mammalian host. Although much has been learned on how Apicomplexa parasites invade host cells inside a PV, little is known of how they rupture the PV membrane and egress host cells. Here, we characterize a Plasmodium protein, called LISP1 (liver-specific protein 1), which is specifically involved in parasite egress from hepatocytes. LISP1 is expressed late during parasite development inside hepatocytes and locates at the PV membrane. Intracellular parasites deficient in LISP1 develop into hepatic merozoites, which display normal infectivity to erythrocytes. However, LISP1-deficient liver-stage parasites do not rupture the membrane of the PV and remain trapped inside hepatocytes. LISP1 is the first Plasmodium protein shown by gene targeting to be involved in the lysis of the PV membrane.