GPI-anchor synthesis

The glycosyl phosphatidylinositol (GPI) anchor of membrane proteins is widely distributed in eukaryotes and parasitic protozoa. The structure and biosynthetic pathway of its core have been elucidated and appear to be conserved in various species. Some of the genes involved in mammalian GPI-anchor biosynthesis have recently been isolated using GPI-anchor-deficient mutant cell lines and expression cloning methods. One of these genes proved to be responsible for a GPI-anchor deficiency known as paroxysmal nocturnal hemoglobinuria. Since the core of the GPI anchor is variously modified in different species and since there may be other differences between its biosynthetic pathway in parasites and their hosts, this pathway could be a target for chemotherapy. In this review, Taroh Kinoshita and Junji Takeda focus on the GPI-anchor biosynthetic pathway and the genes involved in it.