Schachter H (2009) Carbohydr Res "Paucimannose N-glycans in Caenorhabditis elegans and Drosophila melanogaster."

Schachter H

[Carbohydr Res, 2009]

There is a rich diversity of paucimannose N-glycans in worms and flies, and these may play a role in the survival of these organisms. Although paucimannose N-glycans are not expressed in vertebrates, complex N-glycans may take over some of the functions of paucimannose N-glycans. Identification of the target proteins of beta-1,2-N-acetylglucosaminyltransferase I (GnTI) in worms and flies and elucidation of their functions may thus lead to a better understanding of the role of GnTI-dependent glycoproteins in the survival/longevity of both invertebrates and vertebrates.

Schachter H (2009) Trends Glycosci Glycotechnol "The functions of paucimannose N-glycans in Caenorhabditis elegans"

Schachter H

[Trends Glycosci Glycotechnol, 2009]

Caenorhabditis elegans makes about 150 individual N-glycan structures. This review discusses the synthesis and possible functions of the paucimannose N-glycans that are highly abundant in invertebrates but not in vertebrates. The complexity of the worm's N-glycans is due in part to a variety of unusual fucosylation reactions and the addition of phosphorylcholine. Phosphorylcholine has been recognized as a widespread antigenic determinant in many important disease-causing parasites. The synthesis of paucimannose N-glycans depends on the prior action of UDP-GlcNAc:alpha 3-D-mannoside beta 1,2-N-acetylglucosaminyltransferase I (GnTI, encoded by Mgat1). There are three GnTI isoenzymes in the worm (GLY-12, GLY-13, GLY-14). Each GnTI isoenzyme has a distinct set of target proteins and a distinct role in the interaction of C.elegans with pathogenic bacteria. Identification of the protein substrates of GnTI in worms and elucidation of their functions may lead to a better understanding of the role of GnTI-dependent glycoproteins in the survival of both invertebrates and vertebrates.

Polevoda B et al. (2003) J Mol Biol "N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins."

Polevoda B, Sherman F

[J Mol Biol, 2003]

N(alpha)-terminal acetylation occurs in the yeast Saccharomyces cerevisiae by any of three N-terminal acetyltransferases (NAT), NatA, NatB, and NatC, which contain Ard1p, Nat3p and Mak3p catalytic subunits, respectively. The N-terminal sequences required for N-terminal acetylation, i.e. the NatA, NatB, and NatC substrates, were evaluated by considering over 450 yeast proteins previously examined in numerous studies, and were compared to the N-terminal sequences of more than 300 acetylated mammalian proteins. In addition, acetylated sequences of eukaryotic proteins were compared to the N termini of 810 eubacterial and 175 archaeal proteins, which are rarely acetylated. Protein orthologs of Ard1p, Nat3p and Mak3p were identified with the eukaryotic genomes of the sequences of model organisms, including Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana, Mus musculus and Homo sapiens. Those and other putative acetyltransferases were assigned by phylogenetic analysis to the following six protein families: Ard1p; Nat3p; Mak3p; CAM; BAA; and Nat5p. The first three families correspond to the catalytic subunits of three major yeast NATs; these orthologous proteins were identified in eukaryotes, but not in prokaryotes; the CAM family include mammalian orthologs of the recently described Camello1 and Camello2 proteins whose substrates are unknown; the BAA family comprise bacterial and archaeal putative acetyltransferases whose biochemical activity have not been characterized; and the new Nat5p family assignment was on the basis of putative yeast NAT, Nat5p (YOR253W). Overall patterns of N-terminal acetylated proteins and the orthologous genes possibly encoding NATs suggest that yeast and higher eukaryotes have the same systems for N-terminal acetylation.

Paschinger K et al. (2008) Carbohydr Res "The N-glycosylation pattern of Caenorhabditis elegans."

Rendi D, Gutternigg M, Paschinger K, Wilson IB

[Carbohydr Res, 2008]

Determining the exact nature of N-glycosylation in Caenorhabditis elegans, a nematode worm and genetic model organism, has proved to have been an unexpected challenge in recent years; a wide range of modifications of its N-linked oligosaccharides have been proposed on the basis of structural and genomic analysis. Particularly mass spectrometric studies by a number of groups, as well as the characterisation of recombinant enzymes, have highlighted those aspects of N-glycosylation that are conserved in animals, those which are seemingly unique to this species and those which are shared with parasitic nematodes. These data, of importance for therapeutic developments, are reviewed.

Schachter H et al. (2002) Biochem Soc Symp "Functional post-translational proteomics approach to study the role of N-glycans in the development of Caenorhabditis elegans."

Spence AM, Rosa JC, Schachter H, Reinhold VN, Fan XL, Chen SH, Zhang WL, Callahan JW, Mahuran DJ, Bagshaw RD, She YM, Zhu SX

[Biochem Soc Symp, 2002]

Glycosylation is one of the most common post-translational protein modifications. Carbohydrate-mediated interactions between cells and their environment are important in differentiation, embryogenesis, inflammation, cancer and metastasis and other processes. Humans and mice with mutations that prevent normal N-glycosylation show multi-systemic defects in embryogenesis, thereby proving that these molecules are essential for normal development; however, a large number of proteins undergo defective glycosylation in these human and mouse mutants, and it is therefore difficult to determine the precise molecular roles of specific N-glycans on individual proteins. We describe here a 'functional post-translational proteomics' approach that is designed to determine the role of N-glycans on individual glycoproteins in the development of Caenorhabditis elegans.

Luo GZ et al. (2015) Nat Rev Mol Cell Biol "DNA N(6)-methyladenine: a new epigenetic mark in eukaryotes?"

He C, Blanco MA, Luo GZ, Greer EL, Shi Y

[Nat Rev Mol Cell Biol, 2015]

DNA N(6)-adenine methylation (N(6)-methyladenine; 6mA) in prokaryotes functions primarily in the host defence system. The prevalence and significance of this modification in eukaryotes had been unclear until recently. Here, we discuss recent publications documenting the presence of 6mA in Chlamydomonas reinhardtii, Drosophila melanogaster and Caenorhabditis elegans; consider possible roles for this DNA modification in regulating transcription, the activity of transposable elements and transgenerational epigenetic inheritance; and propose 6mA as a new epigenetic mark in eukaryotes.

Paschinger K et al. (2019) Front Mol Biosci "N-glycomic Complexity in Anatomical Simplicity: Caenorhabditis elegans as a Non-model Nematode?"

Yan S, Paschinger K, Wilson IBH

[Front Mol Biosci, 2019]

<i>Caenorhabditis elegans</i> is a genetically well-studied model nematode or &quot;worm&quot;; 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 Man_2-3GlcNAc₂ 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) <i>N-</i>acetylglucosamine. Only some of these modifications are shared with various other nematodes, while others have yet to be detected in any other species. Thus, <i>C. elegans</i> 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.

Struwe WB et al. (2010) Methods Enzymol "High-throughput RNAi screening for N-glycosylation dependent loci in Caenorhabditis elegans."

Warren CE, Struwe WB

[Methods Enzymol, 2010]

The attachment of oligosaccharides to the amide nitrogen of asparagine side chains on proteins is a fundamental process occurring in all metazoans. This process, known as N-glycosylation, is complex and is achieved by the precise interactions of various cellular components. The initial stage of N-glycan biosynthesis is preserved among eukaryotes, and defective enzymes or components in this pathway cause congenital disorders of glycosylation type I (CDG-I) in humans. This disease is rare but exceedingly life-threatening with no known cure. Paramount to CDG treatment and care is understanding the mechanisms of N-glycosylation and factors that influence the pathology of the disease, both of which are not completely known. Here we outline a novel technique to model a CDG-I-like condition and identify genes that are vital for healthy glycosylation in Caenorhabditis elegans. C. elegans is a well-established model for understanding the complexity of glycosylation in development and disease. Although C. elegans N-glycan structures are dissimilar to that observed in higher eukaryotes, they contain over 150 gene homologs that are directly involved in glycosylation. Moreover, the annotated genome of C. elegans, its susceptibility to genetic silencing and its recognizable phenotypes, is a suitable model to dissect the complex phenomenon of glycosylation and identify genes that are required for N-glycan biosynthesis.

Joza N et al. (2009) Ann N Y Acad Sci "AIF: not just an apoptosis-inducing factor."

Kroemer G, Penninger JM, Modjtahedi N, Hangen E, Joza N, Pospisilik JA, Hanada T

[Ann N Y Acad Sci, 2009]

Since its discovery nearly a decade ago, apoptosis-inducing factor (AIF) has had anything but a staid and uneventful existence. AIF was originally described as a mitochondrial intermembrane protein that, after apoptosis induction, can translocate to the nucleus and trigger chromatin condensation and DNA fragmentation. Over the years, an AIF-mediated caspase-independent cell death pathway has been defined. Rather than functioning as a general component of the cell death machinery, AIF is required for specific cell death pathways, including lethal responses to excitotoxins such as N-methyl-D-aspartate and glutamate, the DNA-alkylating agent N-methyl-N'-nitro-N-nitroso-guanidine, hypoxia-ischemia, or growth factor deprivation. Also, important roles of AIF in mitochondrial metabolism and redox control, and more recently in obesity and diabetes, have been discovered. Much of our knowledge has come from studies of AIF orthologs in model organisms, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mice, which have also highlighted the importance of AIF in animal physiology and human pathology. Here, we discuss the manifold nature of AIF in cell life and death, with particular emphasis of its roles in vivo.

Haslam SM et al. (2003) Biochimie "Hallmarks of Caenorhabditis elegans N-glycosylation: complexity and controversy."

Dell A, Haslam SM

[Biochimie, 2003]

Caenorhabditis elegans has become one of the most widely used model organisms for a range of molecular cell biological applications and is being increasingly used by glycobiologists. However, a major problem has been the lack of knowledge of the structure of the protein-linked glycans from this organism. In recent years several groups have published structural data, particularly N-glycan structural data. However, some of these data are contradictory. In this review we critically assess all the N-glycan structural data and consider how close we are in our goal of defining the glycome of C. elegans.