Hallée Stéphanie, Boddey Justin A, Cowman Alan F, Richard Dave
Centre de Recherche en Infectiologie du CHU de Québec-Université Laval, Quebec City, Quebec, Canada.
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
mSphere. 2018 Jan 3;3(1). doi: 10.1128/mSphere.00551-17. eCollection 2018 Jan-Feb.
The rhoptry organelle is critical for the invasion of an erythrocyte by the malaria parasite . Despite their critical roles, the mechanisms behind their biogenesis are still poorly defined. Our earlier work had suggested that the interaction between the glycosylphosphatidylinositol (GPI)-anchored rhoptry-associated membrane antigen (RAMA) and the soluble rhoptry-associated protein 1 was involved in the transport of the latter from the Golgi apparatus to the rhoptry. However, how this protein complex could interact with the intracellular trafficking machinery was unknown at this stage. Here we show that the homologue of the transmembrane protein sortilin-VPS10 interacts with regions of RAMA that are sufficient to target a fluorescent reporter to the rhoptries. These results suggest that sortilin (PfSortilin) could potentially act as the escorter for the transport of rhoptry-destined cargo. The malaria parasite is a massive burden in several parts of the world. Worryingly, the parasite has become resistant to several of the drugs commonly used to treat the disease, and at this time, there is no commercial vaccine. It is therefore critical to identify new targets for the development of antimalarials. To survive in the human body, the malaria parasite needs to invade red blood cells. For this, it uses a variety of effectors stored in organelles forming a structure called the apical complex. The mechanisms behind how the parasite generates the apical complex are poorly understood. In this study, we present evidence that a transmembrane protein called sortilin potentially acts as an escorter to transport proteins from the Golgi apparatus to the rhoptries, a component of the apical complex. Our study provides new insight into the biogenesis of a critical structure of the malaria parasite.
棒状体细胞器对于疟原虫侵入红细胞至关重要。尽管它们起着关键作用，但其生物发生背后的机制仍不清楚。我们早期的研究表明，糖基磷脂酰肌醇（GPI）锚定的棒状体相关膜抗原（RAMA）与可溶性棒状体相关蛋白1之间的相互作用参与了后者从高尔基体向棒状体的转运。然而，在这个阶段，这种蛋白质复合物如何与细胞内运输机制相互作用尚不清楚。在这里，我们表明跨膜蛋白sortilin-VPS10的同源物与RAMA的区域相互作用，这些区域足以将荧光报告蛋白靶向棒状体。这些结果表明，sortilin（PfSortilin）可能作为将注定运往棒状体的货物进行运输的护送蛋白。疟原虫在世界上的几个地区都是巨大的负担。令人担忧的是，这种寄生虫已经对几种常用的治疗该疾病的药物产生了抗性，而且目前还没有商业疫苗。因此，确定抗疟药开发的新靶点至关重要。为了在人体内存活，疟原虫需要侵入红细胞。为此，它使用储存在称为顶复合器的细胞器中的多种效应器。寄生虫如何产生顶复合器背后的机制知之甚少。在这项研究中，我们提供证据表明，一种名为sortilin的跨膜蛋白可能作为护送蛋白，将蛋白质从高尔基体运输到棒状体，棒状体是顶复合器的一个组成部分。我们的研究为疟原虫关键结构的生物发生提供了新的见解。
