Trafficking and sorting of proteins to the parasitophorous vacuolar membrane of the malaria parasite P. falciparum: Exp1 as a model.

疟原虫恶性疟原虫寄生液泡膜上蛋白质的运输和分选：Exp1 作为模型。

• 批准号: 416780686
• 负责人: Professor Dr. Jude Marek Przyborski
• 金额: --
• 依托单位: Professur für Biochemie und Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/416780686?language=en
• 关键词: Trafficking; sorting; proteins; parasitophorous; vacuolar

The human malaria parasite P. falciparum invades and propagates within mature red blood cells. During invasion, the parasite envelops itself within a so-called parasitophorous vacuolar membrane (PVM), which acts as an interface between parasite and host cell, and is implicated in a number of processes important for parasite propagation. To this end, the parasite synthesises a number of proteins which intercalate into the PVM and are essential for parasite survival. However, it is so far unclear how exactly these proteins are both trafficked and sorted from the parasite to the PVM. In this project, using a number of complementary techniques, we aim to address this question and elucidate both the signals and mechanisms utilised to enable protein transport to the PVM. As a model protein, we shall firstly dissect the sorting signals and mechanisms required for the transport of the Exported Protein 1 to the PVM. Principles uncovered during this initial study will then be used to study the trafficking of further PVM-resident proteins such as members of the ETRAMP family. As protein transport to the PVM is a process underlying intra-erythrocytic development of the parasite and the subsequent pathology in the human host, any novel pathways may prove to be a chink in the parasite’s armour which may later be targeted for development of anti-parasitic drugs.

人类疟原虫恶性疟原虫侵入并在成熟的红细胞内繁殖。在入侵过程中，寄生虫将其自身包裹在所谓的寄生虫空泡膜（PVM）中，PVM作为寄生虫和宿主细胞之间的界面，并参与许多对寄生虫繁殖重要的过程。为此，寄生虫合成了许多蛋白质，这些蛋白质插入PVM中，对寄生虫的生存至关重要。然而，目前还不清楚这些蛋白质是如何从寄生虫运输和分选到PVM的。在这个项目中，使用一些互补的技术，我们的目标是解决这个问题，并阐明用于使蛋白质运输到PVM的信号和机制。作为一个模型蛋白，我们将首先剖析出口蛋白1运输到PVM所需的分选信号和机制。在这项初步研究中发现的原则将用于研究进一步的PVM驻留蛋白质，如ETRAMP家族成员的运输。由于蛋白质转运到PVM是寄生虫红细胞内发育和随后人类宿主病理学的基础过程，因此任何新途径都可能被证明是寄生虫盔甲中的裂缝，随后可能成为抗寄生虫药物开发的目标。