Liver-specific protein 2: a Plasmodium protein exported to the hepatocyte cytoplasm and required for merozoite formation
Liver-specific protein 2: a Plasmodium protein exported to the hepatocyte cytoplasm and required for merozoite formation
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DOI：
10.1111/mmi.12083
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发表时间：
2013-01-01
影响因子：
3.6
通讯作者：
Yuda, Masao
中科院分区：
文献类型：
--
作者：
Orito, Yuki;Ishino, Tomoko;Yuda, Masao
肝脏阶段是疟原虫在脊椎动物宿主中复制的第一阶段。然而，很少有人知道的寄生虫肝阶段和它的宿主细胞，肝细胞之间的相互作用。在这项研究中，我们确定了一个出口的蛋白质，在宿主肝细胞寄生虫的发展具有关键作用。伯氏疟原虫肝脏阶段寄生虫的表达序列标签分析表明，转录编码的蛋白质与N-末端信号肽，指定肝脏特异性蛋白2（LISP 2），在这个阶段高度表达。LISP 2的表达在感染后24小时首次观察到，并在肝脏阶段的胚胎发育过程中迅速增加。抗LSP 2抗体免疫荧光染色显示，LISP 2被带到寄生空泡，随后运输到宿主肝细胞的细胞质和细胞核。基因打靶实验表明，大多数的LISP 2突变的肝脏阶段的寄生虫逮捕他们的发展过程中裂殖子的形成。这些结果表明，输出的LISP 2参与肝细胞内肝脏阶段寄生虫发育所需的寄生虫-宿主相互作用。这项研究表明，中晚期肝脏阶段的疟疾寄生虫有一个系统输出蛋白质到宿主细胞的红细胞内阶段，并可能使用蛋白质来修改宿主细胞和改善环境。
The liver stage is the first stage of the malaria parasite that replicates in the vertebrate host. However, little is known about the interplay between the parasite liver stage and its host cell, the hepatocyte. In this study, we identified an exported protein that has a critical role in parasite development in host hepatocytes. Expressed sequence tag analysis of Plasmodium berghei liver-stage parasites indicated that transcripts encoding a protein with an N-terminal signal peptide, designated liver-specific protein 2 (LISP2), are highly expressed in this stage. Expression of LISP2 was first observed 24 h after infection and rapidly increased during the liver-stage schizogony. Immunofluorescent staining with anti-LSP2 antibodies showed that LISP2 was carried to the parasitophorous vacuole and subsequently transported to the cytoplasm and nucleus of host hepatocytes. Gene targeting experiments demonstrated that majority of the LISP2-mutant liver-stage parasites arrested their development during formation of merozoites. These results indicate that exported LISP2 is involved in parasite-host interactions required for the development of liver-stage parasites inside hepatocytes. This study demonstrated that mid-to-late liver-stage malarial parasites have a system for exporting proteins to the host cell as intraerythrocytic stages do and presumably to use the proteins to modify the host cell and improve the environment.