van Dooren Giel G, Reiff Sarah B, Tomova Cveta, Meissner Markus, Humbel Bruno M, Striepen Boris
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, 30602, USA.
Curr Biol. 2009 Feb 24;19(4):267-76. doi: 10.1016/j.cub.2008.12.048. Epub 2009 Feb 12.
Apicomplexan parasites cause numerous important human diseases, including malaria and toxoplasmosis. Apicomplexa belong to the Alveolata, a group that also includes ciliates and dinoflagellates. Apicomplexa retain a plastid organelle (the apicoplast) that was derived from an endosymbiotic relationship between the alveolate ancestor and a red alga. Apicoplasts are essential for parasite growth and must correctly divide and segregate into daughter cells upon cytokinesis. Apicoplast division depends on association with the mitotic spindle, although little is known about the molecular machinery involved in this process. Apicoplasts lack the conserved machinery that divides chloroplasts in plants and red algae, suggesting that these mechanisms are unique.
Here, we demonstrate that a dynamin-related protein in Toxoplasma gondii (TgDrpA) localizes to punctate regions on the apicoplast surface. We generate a conditional dominant-negative TgDrpA cell line to disrupt TgDrpA functions and demonstrate that TgDrpA is essential for parasite growth and apicoplast biogenesis. Fluorescence recovery after photobleaching and time-lapse imaging studies provide evidence for a direct role for TgDrpA in apicoplast fission.
Our data suggest that DrpA was likely recruited from the alveolate ancestor to function in fission of the symbiont and ultimately replaced the conserved division machinery of that symbiont.
顶复门寄生虫引发众多重要的人类疾病，包括疟疾和弓形虫病。顶复门属于囊泡虫类，该类群还包括纤毛虫和甲藻。顶复门保留了一种质体细胞器（顶质体），它源自囊泡虫类祖先与红藻之间的内共生关系。顶质体对于寄生虫的生长至关重要，并且在细胞分裂时必须正确分裂并分配到子细胞中。顶质体的分裂依赖于与有丝分裂纺锤体的关联，尽管对于这一过程中涉及的分子机制知之甚少。顶质体缺乏在植物和红藻中用于分裂叶绿体的保守机制，这表明这些机制是独特的。
在此，我们证明弓形虫中的一种动力蛋白相关蛋白（TgDrpA）定位于顶质体表面的点状区域。我们构建了一个条件性显性负性TgDrpA细胞系以破坏TgDrpA的功能，并证明TgDrpA对于寄生虫生长和顶质体生物发生至关重要。光漂白后的荧光恢复和延时成像研究为TgDrpA在顶质体分裂中的直接作用提供了证据。
我们的数据表明，DrpA可能是从囊泡虫类祖先那里招募来的，用于共生体的分裂，最终取代了该共生体的保守分裂机制。
