Glycoinositolphospholipids, free and as anchors of proteins, in Trypanosoma cruzi

The most important glycoproteins of trypanosomatids are anchored by glycoin ositolphospholipids (GIPLs) to their plasma membrane. In addition, free GIP Ls have been described, for instance the lipopeptidophosphoglycan (LPPG) wh ich is a major component of the surface of T. cruzi epimastigotes. An inosi tolphosphoceramide (IPC) is part of the LPPG and of glycoproteins present i n different stages of T. cruzi. Ceramide was not found in mammal GIPL-ancho rs. The lipid moieties in T. cruzi anchors can be quite variable. However, mo diacylglycerol (DAG) was found in contrast with the African trypanosomes . In GIPLs of epimastigotes collected at the logarithmic phase of growth bo th, 1 -O-hexadecyl-2-O-palmitoylglycerol and ceramide were identified. Lign oceroylsphinganine is the major ceramide, however, no lignoceric acid was d etected when analysing the candidate precursors IPCs, in any of the stages of T. cruzi. An alkylglycerol has been found either as a lyse species in th e Tc85 glycoprotein of trypomastigotes or acylated as in the 1G7 anchor of metacyclic forms and in the mucins of epimastigote forms. The lipid in the mucins is replaced by ceramide when the parasite differentiates to metacycl ic forms. Also, in the Ssp-4 glycoprotein characteristic of amastigotes, a ceramide was identified as the anchor lipid. These variations suggest that a remodelling mechanism is working in T. cruzi. On the other hand, the olig osaccharide core in the GIPLs of T. cruzi is substituted with galactofurano se, This monosaccharide is found only in the pyranose configuration in mamm alian glycoproteins and glycolipids. Thus, the biosynthetic steps for the i ntroduction of galactofuranose and ceramide in the anchors of T. cruzi are good targets for the development of therapeutic agents.