Author: Jasmeen S. Merzaban

Publisher: Frontiers Media SA

Published: 2020-05-26

Total Pages: 205

ISBN-13: 2889636968

Glycans represent a major constituency of post-translational modifications that occur on most, if not all, proteins. Whether on mammalian or invertebrate cell surfaces, they exist as sugar chain moieties designed from the exquisite and coordinated activity of cell-specific glycosylation. Some of the more common glycan structures are linked to cell surface polypeptides via an asparagine (N)-linked residue or a serine/threonine (O)-linked residue, along with a notable contingent found linked to ceramides in the lipid bilayer known as glycosphingolipids. These glycans can associate with complementary glycan-binding proteins (GBP) or lectins to mediate and translate this carbohydrate recognition to cell function. In immunity, there is increasing evidence that precise immune cell glycans are recognized by corresponding GBPs in a cell-intrinsic or -extrinsic manner. Unique carbohydrate recognition domains within GBPs are comprised of precisely spaced amino acid functional groups that allow for selective engagement of a particular glycan target. This structure-function relationship is present in immune signaling pathways, whereby glycans and GBPs on the surface of immune cells (and non-immune cells) help control processes such as immune cell activation, recognition of pathogens, suppression and tissue-specific migration. The diversity of glycan structures and glycosylation among individual immune cell subsets is controlled by the expression of genes involved in glycan biosynthesis including glycosyltransferases, glycosidases, glycan-precursor biosynthetic enzymes and nucleotide-sugar transporters. These genes represent more than 3% of the human genome, and cell-specific expression of these genes dictates a cell’s glycan repertoire, ultimately influencing its molecular interactions with GBPs. Altogether, these emerging lines of investigation highlight the regulatory capacity of glycans in immune health and disease, which in turn, pave the way for novel diagnostic, prognostic, and therapeutic strategies.