Life is sweet: the cell biology of glycoconjugates

Abstract

Cells are dazzling in their diversity, both within and across organisms. And yet, throughout this variety runs at least one common thread: sugars. All cells on Earth, in all domains of life, are literally covered in glycans, a term referring to the carbohydrate portion of glycoproteins and glycolipids. In spite of (or, perhaps, because of) their tremendous structural and functional complexity, glycans have historically been underexplored compared with other areas of cell biology. Recently, however, advances in experimental systems and analytical methods have ushered in a renaissance in glycobiology, the study of the biosynthesis, structures, interactions, functions, and evolution of glycans. Today, glycobiology is poised to make major new contributions to cell biology and become more fully integrated into our understanding of cell and organismal physiology.

FIGURE 1:

Diversity of glycans. (A) Stereochemistry can greatly affect the physical and biological properties of glycans, as exemplified by the differences between glycogen (left) and cellulose (right), both polymers of 1,4-linked glucose. The glycosidic bonds are highlighted in yellow. (B) Glycan diversity is increased by branching. For example, in a mammalian N-glycan, a mannose residue (shown) might be linked to another mannose or an N-acetylglucosamine (GlcNAc) at its 1, 2, 3, 4, or 6 carbon position. (C) Postsynthetic modifications further diversify glycans. Here, a heparan sulfate disaccharide is pictured with arrows indicating known sites of possible sulfation. (D) Major classes of animal glycans are depicted. Most glycan types reside on the cell surface or in the extracellular space (here shown above the membrane). O-GlcNAc is intracellular, modifying nuclear and cytoplasmic proteins (below the membrane). (E) A given protein can exist in multiple glycoforms within a single cell or tissue, a phenomenon referred to as microheterogeneity. (F) A given protein can exist in distinct glycoforms across different tissues or organs, a phenomenon referred to as macroheterogeneity. (G) A single glycosylation site at Ser-49 is required for the assembly of the cytoskeletal protein vimentin into intermediate filaments in human cells. Interestingly, the same residue is dispensable for filament assembly in vitro, indicating an in vivo regulatory role for glycosylation at this site. Here, wild-type or unglycosylatable Ser-49-Ala mutant vimentin-GFP was expressed in vimentin^−/− HeLa cells and imaged by fluorescence microscopy, as described in Tarbet et al. (2018).