Ferguson M A, Brimacombe J S, Cottaz S, Field R A, Güther L S, Homans S W, McConville M J, Mehlert A, Milne K G, Ralton J E
Department of Biochemistry, University of Dundee, U.K.
Parasitology. 1994;108 Suppl:S45-54. doi: 10.1017/s0031182000075715.
The glycosyl-phosphatidylinositol (GPI) protein-membrane anchors are ubiquitous among the eukaryotes. However, while mammalian cells typically express in the order of 100 thousand copies of GPI-anchor per cell, the parasitic protozoa, particularly the kinetoplastids, express up to 10-20 million copies of GPI-anchor and/or GPI-related glycolipids per cell. Thus GPI-family members dominate the cell surface molecular architecture of these organisms. In several cases, GPI-anchored proteins, such as the variant surface glycoprotein (VSG) of the African trypanosomes, or GPI-related glycolipids, such as the lipophosphoglycan (LPG) of the Leishmania, are known to be essential for parasite survival and infectivity. The highly elevated levels and specialised nature of GPI metabolism in the kinetoplastid parasites suggest that the GPI biosynthetic pathways might be good targets for the development of chemotherapeutic agents. This article introduces the range of GPI structures found in protozoan parasites, and their mammalian hosts, and discusses some aspects of GPI biosynthesis.
糖基磷脂酰肌醇(GPI)蛋白-膜锚在真核生物中普遍存在。然而,哺乳动物细胞通常每个细胞表达约10万个GPI锚,而寄生原生动物,特别是动基体目生物,每个细胞表达多达1000万至2000万个GPI锚和/或GPI相关糖脂。因此,GPI家族成员主导了这些生物体的细胞表面分子结构。在一些情况下,已知GPI锚定蛋白,如非洲锥虫的可变表面糖蛋白(VSG),或GPI相关糖脂,如利什曼原虫的脂磷壁酸(LPG),对寄生虫的存活和感染性至关重要。动基体目寄生虫中GPI代谢的高度升高水平和特殊性质表明,GPI生物合成途径可能是开发化疗药物的良好靶点。本文介绍了原生动物寄生虫及其哺乳动物宿主中发现的GPI结构范围,并讨论了GPI生物合成的一些方面。