N-glycosylation in trypanosomatid protozoa.

Abstract

Trypanosomatid protozoa are parasites of considerable medical and economic importance in developing countries. The pathway leading to N-glycosylation in these microorganisms is characterized by the following features: (i) dolichols are composed of only 10-13 isoprene units; (ii) oligosaccharides transferred in N-glycosylation have the compositions Man(6,7,9)GlcNAc2, depending on the species; (iii) trypanosomatids are unable to synthesize dolichol-P-Glc and, in addition, some species lack certain dolichol-P-Man-dependent mannosyltransferases; (iv) the oligosaccharyltransferase does not require the presence of glucose units in the oligosaccharide in order to catalyse an efficient transfer reaction; (v) trypanosomatids have a glucosidase II-like enzyme, but lack glucosidase I; (vi) glucosidase II is required for deglucosylation of oligosaccharides glucosylated by the UDP-Glc:glycoprotein glucosyltransferase, an activity first detected in those parasites; (vii) the structures of polymannose-type compounds in these protozoa have no significant differences with those of their mammalian counterparts except for the presence, in certain species, of oligosaccharides having galactofuranose units linked to external mannose residues; (viii) biantennary complex-type oligosaccharides having in some cases terminal alpha-linked galactose units or poly-N-acetylactosamine extensions, but lacking sialic acid units, have been described in Trypanosoma brucei; (ix) complex-type oligosaccharides having alpha-linked galactose, fucose and sialic acid residues have been described in Trypanosoma cruzi. In this parasite, addition of sialic acid units to glycoproteins and glycolipids is mediated by a trans-sialidase located on the external surface of the parasite and not by an intracellular CMP-sialic acid-dependent sialyltransferase.