Glycosylation of Caenorhabditis elegans III

The model organism, Caenorhabditis elegans, is much studied at the genetic level; however, its glycosylation - a set of key modifications of all cell surfaces - is still poorly understood. Recent data from this and other laboratories suggest that the carbohydrates covalently-bound to nematode glycoproteins share some basic features with those found in mammals, but have some novel decorations. In particular, the presence of asparagine-linked glycan structures with up to four fucose residues and two O-methyl substitutions, as well as phosphorylcholine, is highly intriguing. Some of these features are shared, at least in part, by parasitic nematodes and so Caenorhabditis elegans is potentially a useful model for developing novel strategies in the study of these types of oligosaccharides with potential benefits in combatting nematode parasites. In the proposed study, it is intended to continue a long-term study on the biosynthesis and structure of the N-glycans of Caenorhabditis. In particular, using glycan analysis of double glycomutants, assays of a novel fucosyltransferase and the use of a chemical probe for fucosylation as well as a comparison with nematode parasites of plants, a variety of biochemical and analytical tools will be employed so as to uncover aspects of the molecular basis for multiple fucosylation events in the model nematode; the potential implications are to identify enzymes generating unusual glycan structures which in parasitic organisms may play roles in host-parasite interactions.

The model organism, Caenorhabditis elegans, is much studied at the genetic level; however, its glycosylation - a set of key modifications of all cell surfaces - is still poorly understood. Recent data from this and other laboratories suggest that the carbohydrates covalently-bound to nematode glycoproteins share some basic features with those found in mammals, but have some novel decorations. In particular, the presence of asparagine-linked glycan structures with up to four fucose residues and two O-methyl substitutions, as well as phosphorylcholine, is highly intriguing. Some of these features are shared, at least in part, by parasitic nematodes and so Caenorhabditis elegans is potentially a useful model for developing novel strategies in the study of these types of oligosaccharides with potential benefits in combatting nematode parasites. In this project, a long-term study on the biosynthesis and structure of the N-glycans of Caenorhabditis was continued. In particular, using glycan analysis of double and triple glycomutants, assays of a novel fucosyltransferase and a comparison with other nematodes, a variety of biochemical and analytical tools were employed to uncover aspects of the molecular basis for multiple fucosylation events in the model nematode. Novel aspects of nematode Nglycans were revealed and also comparisons to insects could be made. The potential future implications are to identify enzymes generating unusual glycan structures which in parasitic organisms may play roles in host-parasite interactions.