Spatiotemporal diversity and regulation of glycosaminoglycans in cell homeostasis and human disease

Glycosaminoglycans (GAGS) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates play important roles in many cellular processes and have been implicated in many disease states, including cancer, inflammation, and genetic disorders. GAGs are among the most complex molecules in biology with enormous information content and extensive structural and functional heterogeneity. GAG biosynthesis is a nontemplate-driven process facilitated by a large group of biosynthetic enzymes that have been extensively characterized over the past few decades. Interestingly, the expression of the enzymes and the consequent structure and function of the polysaccharide chains can vary temporally and spatially during development and under certain pathophysiological conditions, suggesting their assembly is tightly regulated in cells. Due to their many key roles in cell homeostasis and disease, there is much interest in targeting the assembly and function of GAGs as a therapeutic approach. Recent advances in genomics and GAG analytical techniques have pushed the field and generated new perspectives on the regulation of mammalian glycosylation. This review highlights the spatiotemporal diversity of GAGs and the mechanisms guiding their assembly and function in human biology and disease.

Automated summary

Glycosaminoglycans (GAGs) are long polysaccharides found on the cell surface and extracellular matrix of animal cells, and play important roles in cellular processes and diseases. GAGs are complex molecules with extensive structural and functional heterogeneity, and their biosynthesis is a non-template driven process involving a group of enzymes. Due to their key roles in cell homeostasis and disease, targeting the assembly and function of GAGs is of great interest as a therapeutic approach.