PROTEIN TARGETING TO AND THROUGH THE T GONDII PVM

描述(摘自摘要)：弓形虫是主要的 艾滋病患者局部中枢神经系统感染的原因。T. 弓形虫是顶端复合体寄生虫家族的成员，该家族包括 隐孢子虫和疟原虫，所有这些物种都是专性的 胞内寄生虫。对于弓形虫和疟原虫，液泡是 周围有一层特殊的膜，称为寄生液泡 膜(PVM)，它是寄生虫和宿主之间的界面 手机。尽管弓形虫PVM的选定特征是 理解，其他功能定义更明确和/或更易于学习 被疟原虫感染的红细胞。尤其是生物合成， 跨膜蛋白EXP-1的运输和随后的拓扑结构 在恶性疟原虫内建立了PVM，它是一种 可溶蛋白质的子集(包括血糖素结合蛋白，或GBP) 穿过PVM进入红细胞胞浆。为了方便我们的 使用为研究弓形虫而开发的工具，了解弓形虫PVM。 关于感染恶性疟原虫的红细胞，调查人员建议：(1) 鉴定在弓形虫中表达的EXP-1的拓扑结构，并确定 该蛋白在弓形虫中的亚细胞定位和转运 感染细胞，以及(2)鉴定运输的弓形虫蛋白 通过PVM进入宿主细胞胞浆，并探讨其机制 在这个过程中。这些实验将同时提供洞察力 对弓形虫PVM的结构和功能进行研究，并将描绘 两者PVM的异同之处 寄生虫。这是一家拥有专业知识的美国实验室与 弓形虫生物学和一个具有疟原虫专业知识的德国实验室 生物学将促进我们对寄生虫和寄生虫PVM的理解 对药物进入细胞内的生物体具有潜在的意义。

DESCRIPTION (adapted from the ABSTRACT): Toxoplasma gondii is the leading cause of local central nervous system infections in patients with AIDS. T. gondii is a member of the apicomplexan family of parasites, which includes crytosporidium and plasmodium species, all of which are obligate intracellular parasites. For Toxoplasma and Plasmodia, the vacuole is surrounded by a specialized membrane, termed the parasitophorous vacuole membrane (PVM), which is the interface between the parasite and the host cell. Although selected characteristics of the T. gondii PVM are understood, other features are more well defined and/or easier to study in plasmodium-infected erythrocytes. In particular, the biosynthesis, transport, and subsequent topology of the transmembrane protein EXP-1 within the P. falciparum PVM is established, and is the transport of a subset of soluble proteins (including glycophorin-binding protein, or GBP) across the PVM and into the erythrocyte cytosol. To facilitate our understanding of the T. gondii PVM, using tools developed to study P. falciparum-infected erythrocytes, the Investigator proposes to: (1) identify the topology of EXP-1 expressed in Toxoplasma and determine the subcellular localization and transport of the protein in T. gondii- infected cells, and (2) identify T. gondii proteins which are transported across the PVM and into the host cell cytosol and explore the mechanism for this process. These experiment will simultaneously provide insight into the structure and function of the T. gondii PVM and will delineate both the similarities and differences between the PVM in the two parasites. This collaboration between a U.S. laboratory with expertise in T. gondii biology and a german laboratory with expertise in Plasmodia biology will foster our understanding of the PVM of both parasites and have implication for drug delivery into the intracellular organisms.