Characterization of the ATG8-conjugation system in 2 Plasmodium species with special focus on the liver stage Possible linkage between the apicoplastic and autophagic systems?
Characterization of the ATG8-conjugation system in 2 Plasmodium species with special focus on the liver stage Possible linkage between the apicoplastic and autophagic systems?
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DOI：
10.4161/auto.27166
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发表时间：
2014-02-01
期刊：
影响因子：
13.3
通讯作者：
Coppens, Isabelle
中科院分区：
文献类型：
--
作者：
Jayabalasingham, Bamini;Voss, Christiane;Coppens, Isabelle
疟原虫寄生虫成功地在哺乳动物和蚊子的不同栖息地定居，适应各种环境伴随着其细胞器组成和大小的变化。以前，我们观察到，在肝细胞感染，疟原虫丢弃细胞器参与入侵和扩大那些参与生物合成途径。我们假设这一过程是由自噬调控的。疟原虫属拥有一套基本的已知自噬相关蛋白，包括酵母Atg 8的直系同源物。在这项研究中，我们分析了ATG 8结合途径的活动过程中的恶性疟原虫的生命周期和伯氏疟原虫的肝脏阶段。我们工程化了表达mCherry-PfATG 8的转基因恶性疟原虫菌株。这些转基因寄生虫在人肝细胞和红细胞以及按蚊的中肠和唾液腺中表达mCherry-PfATG 8。在所有观察到的阶段中，mCherry-PfATG 8定位于管状结构。我们在伯氏疟原虫中进行的EM和共定位研究表明，PbATG 8与内共生体衍生的质体样细胞器（称为顶质体）的限制膜相关。有趣的是，在肝细胞中的寄生虫复制期间，PbATG 8与顶质体的关联随着该细胞器尺寸的扩大而增加。PbATG 3、PbATG 7和PbATG 8在所有寄生阶段都是共转录的。PbATG 8和PbATG 3的分子分析揭示了一种新的相互作用机制，与其他直向同源物相比。这进一步得到疟原虫ATG 8不能在功能上补充atg 8酵母或定位于饥饿哺乳动物细胞中的自噬体的支持。总之，这些数据表明了一个独特的作用，在疟原虫ATG 8共轭系统。
Plasmodium parasites successfully colonize different habitats within mammals and mosquitoes, and adaptation to various environments is accompanied by changes in their organelle composition and size. Previously, we observed that during hepatocyte infection, Plasmodium discards organelles involved in invasion and expands those implicated in biosynthetic pathways. We hypothesized that this process is regulated by autophagy. Plasmodium spp. possess a rudimentary set of known autophagy-related proteins that includes the ortholog of yeast Atg8. In this study, we analyzed the activity of the ATG8-conjugation pathway over the course of the lifecycle of Plasmodium falciparum and during the liver stage of Plasmodium berghei. We engineered a transgenic P. falciparum strain expressing mCherry-PfATG8. These transgenic parasites expressed mCherry-PfATG8 in human hepatocytes and erythrocytes, and in the midgut and salivary glands of Anopheles mosquitoes. In all observed stages, mCherry-PfATG8 was localized to tubular structures. Our EM and colocalization studies done in P. berghei showed the association of PbATG8 on the limiting membranes of the endosymbiont-derived plastid-like organelle known as the apicoplast. Interestingly, during parasite replication in hepatocytes, the association of PbATG8 with the apicoplast increases as this organelle expands in size. PbATG3, PbATG7 and PbATG8 are cotranscribed in all parasitic stages. Molecular analysis of PbATG8 and PbATG3 revealed a novel mechanism of interaction compared with that observed for other orthologs. This is further supported by the inability of Plasmodium ATG8 to functionally complement atg8 yeast or localize to autophagosomes in starved mammalian cells. Altogether, these data suggests a unique role for the ATG8-conjugation system in Plasmodium parasites.