ARCHITECTURE OF MEMBRANE SYSTEMS IN PLASMODIUM FALCIPARUM-INFECTED ERYTHROCYTES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 恶性疟原虫导致人类最严重的疟疾形式，并 每年造成约200万人死亡(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。这些蛋白质 能够使红细胞附着在血管上的物质是由寄生虫合成的， 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，寄生虫产生了新的 宿主细胞胞质内的结构，以调节蛋白质的运输。这些措施包括 被称为毛雷尔-S裂隙(MC)的隔室在 将寄生虫蛋白质运送到宿主细胞表面。大约三分之一的人 在其48小时的红细胞内循环中，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对细胞的粘附 血管内皮细胞，导致感染的红细胞在器官中积聚 如大脑和胎盘，这可能是致命的(Kyes等人，1999年)。这些蛋白质可以 也可以结合和抑制树突状细胞的成熟，并可能调节免疫 答复(Urban等人，1999年)。这个项目的一个主要目标是增加我们的 对结构的组织、形态和功能的理解 毛尔？S裂开了。这些细胞器是由寄生虫在宿主体内从头开始形成的。 S细胞质，被认为参与了蛋白质向 被感染的红细胞的表面。更好地了解MC和运输 进出MC的不同组件可能会导致新的 中断毒力因子贩运和传递的抗疟疾战略。 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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.