Evidence for a Golgi-to-Endosome Protein Sorting Pathway in Plasmodium falciparum

During the asexual intraerythrocytic stage, the malaria parasite Plasmodium falciparum must traffic newly-synthesized proteins to a broad array of destinations within and beyond the parasite's plasma membrane. In this study, we have localized two well-conserved protein components of eukaryotic endosomes, the retromer complex and the small GTPase Rab7, to define a previously-undescribed endosomal compartment in P. falciparum. Retromer and Rab7 co-localized to a small number of punctate structures within parasites. These structures, which we refer to as endosomes, lie in close proximity to the Golgi apparatus and, like the Golgi apparatus, are inherited by daughter merozoites. However, the endosome is clearly distinct from the Golgi apparatus as neither retromer nor Rab7 redistributed to the endoplasmic reticulum upon brefeldin A treatment. Nascent rhoptries (specialized secretory organelles required for invasion) developed adjacent to endosomes, an observation that suggests a role for the endosome in rhoptry biogenesis. A P. falciparum homolog of the sortilin family of protein sorting receptors (PfSortilin) was localized to the Golgi apparatus. Together, these results elaborate a putative Golgi-to-endosome protein sorting pathway in asexual blood stage parasites and suggest that one role of retromer is to mediate the retrograde transport of PfSortilin from the endosome to the Golgi apparatus.

在无性红细胞内期，恶性疟原虫（Plasmodium falciparum）需将新合成的蛋白质转运至虫体质膜内外的多种不同位点。本研究中，我们对真核生物内体（endosome）的两个高度保守蛋白组分——分选蛋白复合物（retromer complex）与小GTP酶Rab7（small GTPase Rab7）进行了定位，以此解析恶性疟原虫中此前未被描述的内体区室。分选蛋白复合物与Rab7共定位于虫体内少量点状结构中。我们将此类结构命名为内体，它们紧邻高尔基体（Golgi apparatus），且与高尔基体一样，可被子代裂殖子所继承。不过，内体与高尔基体存在显著差异：经布雷菲德菌素A（brefeldin A）处理后，分选蛋白复合物与Rab7均不会重新分布至内质网（endoplasmic reticulum）。新生棒状体（rhoptries，侵袭过程必需的特化分泌细胞器）在靠近内体的位置形成，这一现象提示内体可能参与棒状体的生物发生过程。恶性疟原虫的蛋白分选受体分拣蛋白（sortilin）家族同源物PfSortilin被定位于高尔基体。综上，本研究结果阐明了无性血液期疟原虫中一条潜在的高尔基体→内体蛋白分选通路，并提示分选蛋白复合物的功能之一是介导PfSortilin从内体逆向转运至高尔基体。