ARCHITECTURE OF MEMBRANE SYSTEMS IN PLASMODIUM FALCIPARUM-INFECTED ERYTHROCYTES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 恶性疟原虫是人类最严重的疟疾病原体，造成约200万人感染。 每年的死亡人数(Snow等人，2005年)。死亡主要是由于一种称为脑型疟疾的并发症，在这种并发症中，感染了 红血球(RBC)附着在大脑的血管壁上。使红细胞与血液黏附的蛋白质 血管是由寄生虫合成的，并被运送到红细胞表面。这是一个令人印象深刻的壮举，因为RBC 没有贩卖机器。为了做到这一点，寄生虫在宿主细胞细胞质中产生新的结构 来调节蛋白质的运输。这些包括被称为毛雷氏裂隙(MC)的隔室，它们在 寄生虫蛋白向宿主细胞表面的运输。在48小时中，大约有三分之一的路程 在红血球周期内，寄生虫来源的毒力蛋白被插入红细胞膜。这些蛋白质可以 介导与血管内皮细胞的黏附，导致感染的红细胞在脑等器官中积聚 和胎盘，这可能是致命的(Kyes等人，1999年)。这些蛋白还可以结合和抑制树突状细胞的成熟。 并可能调节免疫反应(Urban等人，1999)。这个项目的一个主要目标是增加我们的 了解被称为毛雷氏裂的结构的组织、形态和功能。这些细胞器 由寄生虫在其宿主细胞的细胞质中从头形成，被认为参与了将蛋白质输送到 受感染的红细胞表面。更好地了解MC以及不同部件的往返运输 MC可能导致开发新的抗疟疾策略，以中断毒力的贩运和传递 各种因素。这可以防止感染的红细胞与血管内皮细胞或未感染的红细胞黏附。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Plasmodium falciparum causes the most severe form of human malaria and is responsible for approximately two million deaths per year (Snow et al., 2005). Deaths are due mainly to a complication known as cerebral malaria, in which infected red blood cells (RBCs) adhere to the walls of blood vessels in the brain. The proteins that enable RBCs to adhere to blood vessels are synthesized by the parasite and transported to the RBC surface. This is an impressive feat given that the RBC is devoid of trafficking machinery. To accomplish this, the parasite generates novel structures within the host cell cytoplasm to mediate protein transport. These include compartments called the Maurer's clefts (MC), which play an important role in the trafficking of parasite proteins to the surface of the host cell. About one third of the way through its 48 hour intraerythrocytic cycle, parasite-derived virulence proteins are inserted into the RBC membrane. These proteins can mediate adhesion to the vascular endothelium, resulting in the accumulation of infected RBCs in organs such as the brain and placenta, which can be lethal (Kyes et al., 1999). These proteins can also bind and inhibit maturation of dendritic cells and may modulate the immune response (Urban et al., 1999). It is a major aim of this project to increase our understanding of the organization, morphology and function of structures known as the Maurer's clefts. These organelles are formed de novo by the parasite in its host cell's cytoplasm and are thought to be involved in the delivery of proteins to the surface of the infected RBC. A better knowledge of the MC and of the transport of different components to and from the MC could lead to the development of new antimalarial strategies that interrupt the trafficking and delivery of virulence factors. This could prevent adhesion of the infected RBCs to the vascular endothelium or uninfected red blood cells.