Mammalian glycosylation in immunity

Abstract

Glycosylation produces a diverse and abundant repertoire of glycans, which are collectively known as the glycome. Glycans are one of the four fundamental macromolecular components of all cells, and are highly regulated in the immune system. Their diversity reflects their multiple biological functions that encompass ligands for proteinaceous of receptors known as lectins. Since the discovery that selectins and their glycan ligands are important for the regulation of leukocyte trafficking, it has been shown that additional features of the vertebrate immune system are also controlled by endogenous cellular glycosylation. This Review focuses on the emerging immunological roles of the mammalian glycome.Glycosylation is the enzymatic process that produces glycosidic linkages of saccharides to other saccharides, proteins and lipids, and is probably as ancient as life itself. Unicellular and multicellular organisms depend on glycosylation to produce monomeric and multimeric glycan linkages that are essential for cell viability and normal function [1][2][3][4] . The resulting glycome encompasses a diverse and abundant repertoire of glycans, which are one of the four fundamental macromolecular components of all cells (together with nucleic acids, proteins and lipids) (FIG. 1). Glycans have important biological functions in protein maturation and turnover, cell adhesion and trafficking, and receptor binding and activation [5][6][7][8] .Glycosylation is prominent in the lumen of the endoplasmic reticulum (ER) and in the Golgi apparatus. The cellular repertoire of glycans that are produced by glycosylation in these organelles of the secretory pathway reflects the combinatorial expression of subsets of glycosyltransferase and glycosidase enzymes, of which there are more than 200 in the mammalian genome. The formation and breakdown of glycans are regulated at several levels in the cell. One of the mechanisms involves transcriptional regulation of the genes that encode these enzymes, but others include access to substrates and molecular interactions that alter enzyme localization in the lumen of the ER and Golgi 2,9,10 . Changes in the glycome can occur in response to environmental and genetic stimuli, and are frequently associated with the acquisition of altered cellular phenotypes [1][2][3][4][5][6][7][8][9][10] .Glycosylation also occurs among proteins in the cytoplasm and nucleus through the actions of the Ogt glycosyltransferase, which produces a reversible O-linked β-N-acetylglucosamine NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript physiological processes and disease. In contrast to this intracellular glycosidic bond that is formed by Ogt, secretory glycosylation in the ER and Golgi produces a large structural repertoire, including oligomeric glycan linkages that are presented at the cell surface and in extracellular compartments. Intracellular glycosylation has been reviewed elsewhere and is not discussed further in this Review 12 .Glycosylation can substantially modify the structure ...

Polypeptide binding specificities of Saccharomyces cerevisiae oligosaccharyltransferase accessory proteins Ost3p and Ost6p

“…The precise glycan structures present on a mature protein can influence protein function in a variety of ways and are important in processes including infection, immunity, cancer, and development. [8][9][10][11] Diversification and regulation of OTase activity seems to have occurred by various mechanisms throughout evolution. Organisms including some Nglycosylating bacteria and divergent eukaryotes have multiple single subunit OTase enzymes homologous to the catalytic Stt3p protein.…”

Bacterial chitinases and chitin-binding proteins as virulence factors

“…It has recently been demonstrated that a diverse range of bacterial chitinases hydrolyse GlcNAc-containing model substrates of LacdiNAc and to a lesser extent also LacNAc, though at low rates (Larsen et al, 2011;Murata et (Varki et al, 2009), and are abundant in proteins of the human immune system (Marth & Grewal, 2008). The possibility that bacteria might be using LacNac structures in O-glycans as substrates has been proposed for a commensal of the human gut, Bacteroides thetaiotaomicron (Martens et al, 2008).…”

Mutations of the Ca2+-sensing Stromal Interaction Molecule STIM1 Regulate Ca2+ Influx by Altered Oligomerization of STIM1 and by Destabilization of the Ca2+ Channel Orai1

“…More moderate physiological and pathophysiological changes in immune cell function occur during aging, but also in autoimmunity and cancer. One mechanism to alter immune cell function arises from the degree and pattern of glycosylation in immune cells (19,20). Although many immune cell surface receptors show complex glycosylation patterns, one alternative target to affect immune cell function by changes in glycosylation may involve altering proteins that regulate SOCE.…”