THE DEVELOPMENTAL REGULATION AND BIOSYNTHESIS OF GPI-RELATED STRUCTURES IN LEISHMANIA PARASITES

Most macromolecules on the surface of Leishmania parasites, including the major surface proteins and a complex lipophosphoglycan (LPG) are a nchored to the plasma membrane via GPI glycolipids. Free glycoinositol -phospholipids (GIPLs) which are not linked to protein or phosphoglyca n are also abundant in the plasma membrane. From structural and metabo lic labeling studies it is proposed that most Leishmania species expre ss three distinct pathways of GPI biosynthesis. Some of these pathways (i.e. those involved in the protein and LPG anchor biosynthesis) are down-regulated during the differentiation of the insect (promastigote) stage to the mammalian (amastigote) stage. In contrast, the GIPLs are expressed in high copy number in both developmental stages. Based on analysis of the lipid moieties of the different GPI species it is poss ible that the pathways of GPI anchor and GIPL biosynthesis are located in different subcellular compartments. The relative flux through the GIPL and LPG biosynthetic pathways has been examined in L. major proma stigotes. These studies showed that while the rate of synthesis of the GIPLs and LPG is similar, LPG is shed more rapidly from the plasma me mbrane and has a higher turnover. The possible metabolic relationship between the GIPL and LPG biosynthetic pathways is discussed.