N-glycomic Complexity in Anatomical Simplicity: Caenorhabditis elegans as a Non-model Nematode?

Katharina Paschinger,Shi Yan,Iain B H Wilson

doi:10.3389/fmolb.2019.00009

Abstract

Caenorhabditis elegans is a genetically well-studied model nematode or “worm”; however, its N-glycomic complexity is actually baffling and still not completely unraveled. Some features of its N-glycans are, to date, unique and include bisecting galactose and up to five fucose residues associated with the asparagine-linked Man2−3GlcNAc2 core; the substitutions include galactosylation of fucose, fucosylation of galactose and methylation of mannose or fucose residues as well as phosphorylcholine on antennal (non-reducing) N-acetylglucosamine. Only some of these modifications are shared with various other nematodes, while others have yet to be detected in any other species. Thus, C. elegans can be used as a model for some aspects of N-glycan function, but its glycome is far from identical to those of other organisms and is actually far from simple. Possibly the challenges of its native environment, which differ from those of parasitic or necromenic species, led to an anatomically simple worm possessing a complex glycome.

Highlights

Caenorhabditis elegans is one of the top non-mammalian eukaryotic model organisms and is widely used in developmental and aging studies (Corsi et al, 2015; Maglioni et al, 2016)
The major portion of this structure is modified by N-acetylglucosaminyltransferase I (GlcNAc-TI; designated MGAT1 in many species), which in C. elegans is encoded by three different genes which must all be knocked out in order to abolish GlcNAc-TI activity, resulting in an accumulation of Man5GlcNAc2 as the major component of the N-glycome (Zhu et al, 2004); recently we have found a number of unusual glycans with galactose and/or fucose residues in the relevant triple knock-out (Yan et al, 2018b)
The product of GlcNAc-TI, Man5GlcNAc3, is the substrate especially for Golgi α-mannosidase II, which is conserved in multicellular eukaryotes; the activity of this enzyme has been determined for the C. elegans homolog as well as determining a large shift in the N-glycome in the relevant aman-2 mutant strain (Paschinger et al, 2006)

Summary

INTRODUCTION

Caenorhabditis elegans is one of the top non-mammalian eukaryotic model organisms and is widely used in developmental and aging studies (Corsi et al, 2015; Maglioni et al, 2016). The product of GlcNAc-TI, Man5GlcNAc3, is the substrate especially for Golgi α-mannosidase II, which is conserved in multicellular eukaryotes; the activity of this enzyme has been determined for the C. elegans homolog as well as determining a large shift in the N-glycome in the relevant aman-2 mutant strain (Paschinger et al, 2006). The product of this enzyme is a Man3GlcNAc3 structure (MGn in the Schachter nomenclature), which is the presumed substrate for the two ‘branching’ N-acetylglucosaminyltransferases (GlcNAcTII and GlcNAc-TV; GLY-20 and GLY-2, corresponding to mammalian MGAT2 and MGAT5) as well as Golgi βhexosaminidases HEX-2 and HEX-3 (Chen et al, 2002; Warren et al, 2002b; Zhang et al, 2003; Gutternigg et al, 2007). These early processing events (see Figure 1) to generate either branched N-glycans or the simplest paucimannosidic forms are relatively unspectacular as these or similar reactions occur in a range of other invertebrates including insects

MAXIMAL DEGREE OF

GLYCOSPHINGOLIPIDS AND GLYCOLIPID ANCHORS

GLYCOANALYTICAL CHALLENGES

NUCLEOTIDE SUGAR METABOLISM

ENDOGENOUS AND EXOGENOUS LECTINS

CONCLUSION