The glycoinositolphospholipid profiles of two Leishmania major strains that differ in lipophosphoglycan expression

Abstract

The glycolipid profiles of two Leishmania major strains which differ in their expression of the major glycoconjugate, lipophosphoglycan (LPG), have been compared. All the glycolipids in these strains belong to a class of glycoinositolphospholipids (GIPLs) which can be metabolically labelled with [3H]inositol and are sensitive to phosphatidylinositol-specific phospholipase C. The major glycolipids in the LPG-producing L. major strain V121 are tetraglycosyl phosphatidylinositol (GIPL-1), pentaglycosyl phosphatidylinositol (GIPL-2), hexaglycosyl phosphatidylinositol (GIPL-3) and lyso-GIPL-3. These were identified by their sensitivity to lipases, and by BioGel P4 chromatography of the glycan fragments released after nitrous acid deamination. Similar glycolipids are also present in the LPG-deficient L. major strain LRC-L119. However, this strain also produces several highly polar GIPLs (GIPL-4, 5 and 6) which are absent from V121 and which may represent truncated forms of LPG. Evidence is presented showing that the LPG and GIPLs from both strains contain galactofuranose, based on identification of labelled arabinose after mild periodate oxidation and reduction with NaB [3H]4. Furthermore, analysis of the deaminated glycan moieties after mild acid hydrolysis suggests that the GIPLs and the glycolipid anchor of LPG contain a common glycan core, which includes the galactofuranose. Finally, radiolabelling of intact cells indicates that there is restricted expression of some of the GIPLs in the plasma membrane and that the GIPL-2 is the predominant cell surface glycolipid. These data are consistent with some, but not all, of the GIPLs in V121 having a major role as precursors to the glycolipid core of LPG.