How gene knockouts perturb the N‐glycome of Caenorhabditis elegans (608.3)

Abstract

Although the model nematode Caenorhabditis elegans is considered to be rather simple, its N‐glycome proves to be one of the more complex amongst lower multicellular eukaryotes. Indeed, the number of types and the unusual structure of N‐glycans in this organism seemingly outmatches that of plants or insects. Underlying this is a wealth of glycosyltransferases; as judged by homology, there are well over twenty fucosyltransferases encoded by the worm genome, but the biochemical functionality of only a minority has been assigned. Glycomic analyses would suggest that at least five fucosyltransferases act on N‐glycans of the nematode: beyond the ‘typical’ core α1,3‐ and core α1,6‐fucosyltransferases modifying the distal core N‐acetylglucosamine residue, one fucosyltransferase transfers to the proximal residue of the core, at least one to the periphery of paucimannosidic glycans and at least one to the ‘Galβ1,4Fuc’ epitope. Furthermore, N‐acetylglucosaminyltransferases, processing hexosaminidases and Golgi mannosidase II play an important role in shaping the final N‐glycome. Using a mix of typical assays, glycan microarrays and glycomic analyses of knock‐out strains, we have determined the biochemical function of a number of relevant enzymes. It is also remarkable how novel structures become apparent when analysing the glycomes of ‘multiple‐knock‐out’ strains. Thus, at least under laboratory conditions, a high degree of plasticity of the worm glycome is possible.Grant Funding Source: Austrian Science Fund (FWF) and European Commission (Euroglycanarrays ITN)