Membrane Transport Proteins of the Malaria Parasite

疟疾寄生虫有一个复杂的生命周期，包括细胞内和细胞外阶段，在此期间它遇到了各种环境，许多恶劣的环境。在每个阶段，寄生虫必须有专门的适应，以获取营养，清除可溶的代谢废物，并维持离子梯度。膜运输蛋白可能参与了所有这些过程。膜片钳方法已被用来识别红细胞期的两个离子通道。首先，感染成熟寄生虫的红细胞表面有一条小的(5ps)离子通道。该通道主要对阴离子和少量营养物质具有通透性，可被几种通道阻滞剂抑制(尽管效果不佳)，目前约为2000拷贝/细胞。第二，在细胞内寄生虫周围的膜上有一个单独的大的(150ps)非选择性通道。第二个通道的孔大小为23埃，起到了分子筛的作用，为寄生虫提供了获取红细胞胞浆中可溶营养物质的途径。我们正在努力进一步确定这些通道的特征，并克隆它们的基因。由于它们在寄生虫S适应红细胞中的重要作用，它们可能成为新的通道阻滞剂或疫苗的理想靶点。利用不断增长的疟疾基因组数据库和卵母细胞中的异源表达，也将鉴定寄生虫的其他膜转运蛋白。-疟疾、离子通道、营养素、恶性疟原虫、转运体、膜片钳

The malaria parasite has a complex life cycle with intra- and extra- cellular stages, during which it encounters a variety of environments, many harsh. At each stage, the parasite must have specialized adaptations for acquisition of nutrients, removal of soluble metabolic wastes, and maintenance of ionic gradients. Membrane transport proteins likely mediate all of these. The patch clamp method has been used to identify two of these ion channels for the erythrocytic stage. First, there is a small (5 pS) ion channel on the surface of red cells infected with mature parasites. This channel is primarily permeable to anions and small nutrients, inhibited by several channel blockers (albeit poorly), and is present at ~2000 copies/cell. Second, there is a separate large (150 pS) nonselective channel on the membrane surrounding the intracellular parasite. This second channel has a pore size of 23 angstroms and functions as a molecular sieve, providing the parasite access to soluble nutrients in red cell cytosol. We are working to further characterize these channels and clone their genes. Because of their important roles in the parasite?s adaptation to the red cell, they may be ideal targets for new channel blockers or vaccines.Other membrane transporters of the parasite will also be identified by using the growing malaria genome database and heterologous expression in oocytes. - Malaria, ion channels, nutrients, Plasmodium falciparum, transporters, patch clamp