Morlon-Guyot Juliette, Pastore Sandra, Berry Laurence, Lebrun Maryse, Daher Wassim
Dynamique des Interactions Membranaires Normales et Pathologiques, UMR5235 CNRS, Université Montpellier, Montpellier, France.
Cell Microbiol. 2015 Aug;17(8):1157-78. doi: 10.1111/cmi.12426. Epub 2015 Mar 12.
Apicomplexan parasites harbour unique secretory organelles (dense granules, rhoptries and micronemes) that play essential functions in host infection. Toxoplasma gondii parasites seem to possess an atypical endosome-like compartment, which contains an assortment of proteins that appear to be involved in vesicular sorting and trafficking towards secretory organelles. Recent studies highlighted the essential roles of many regulators such as Rab5A, Rab5C, sortilin-like receptor and syntaxin-6 in secretory organelle biogenesis. However, little is known about the protein complexes that recruit Rab-GTPases and SNAREs for membrane tethering in Apicomplexa. In mammals and yeast, transport, tethering and fusion of vesicles from early endosomes to lysosomes and the vacuole, respectively, are mediated by CORVET and HOPS complexes, both built on the same Vps-C core that includes Vps11 protein. Here, we show that a T. gondii Vps11 orthologue is essential for the biogenesis or proper subcellular localization of secretory organelle proteins. TgVps11 is a dynamic protein that associates with Golgi endosomal-related compartments, the vacuole and immature apical secretory organelles. Conditional knock-down of TgVps11 disrupts biogenesis of dense granules, rhoptries and micronemes. As a consequence, parasite motility, invasion, egress and intracellular growth are affected. This phenotype was confirmed with additional knock-down mutants of the HOPS complex. In conclusion, we show that apicomplexan parasites use canonical regulators of the endolysosome system to accomplish essential parasite-specific functions in the biogenesis of their unique secretory organelles.
顶复门寄生虫拥有独特的分泌细胞器（致密颗粒、棒状体和微线体），这些细胞器在宿主感染中发挥着重要作用。刚地弓形虫寄生虫似乎拥有一个非典型的类似内体的区室，其中包含一系列似乎参与囊泡分选和向分泌细胞器运输的蛋白质。最近的研究强调了许多调节因子，如Rab5A、Rab5C、类sortilin受体和 syntaxin-6在分泌细胞器生物发生中的重要作用。然而，对于在顶复门中募集Rab-GTP酶和SNAREs进行膜拴系的蛋白质复合物却知之甚少。在哺乳动物和酵母中，分别从早期内体到溶酶体和液泡的囊泡运输、拴系和融合是由CORVET和HOPS复合物介导的，这两种复合物都建立在包含Vps11蛋白的相同Vps-C核心上。在这里，我们表明刚地弓形虫Vps11直系同源物对于分泌细胞器蛋白的生物发生或正确的亚细胞定位至关重要。TgVps11是一种动态蛋白，与高尔基体-内体相关区室、液泡和未成熟的顶端分泌细胞器相关联。条件性敲低TgVps11会破坏致密颗粒、棒状体和微线体的生物发生。因此，寄生虫的运动性、侵袭、逸出和细胞内生长都会受到影响。这种表型在HOPS复合物的其他敲低突变体中得到了证实。总之，我们表明顶复门寄生虫利用内溶酶体系统的典型调节因子来完成其独特分泌细胞器生物发生中基本的寄生虫特异性功能。
