Biosynthesis and function of chondroitin sulfate

Abstract

Background: Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions.

Scope of review: Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo.

Major conclusions: Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes.

General significance: Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders.

Keywords: Biosynthesis/catabolism; C4ST; C6ST; CS; ChABC; ChGn; ChPF; ChSy; Chn; Chondroitin sulfate; D4ST; DS; DS-epi; EXT; EXT-like; EXTL; FAM; GAG; Gal; GalNAc; GalNAc 4-sulfate 6-O-sulfotransferase; GalNAc transferase; GalNAc4S-6ST; GalNAcT; GalT-I; GalT-II; GlcA; GlcA C-5 epimerase (DS epimerase); GlcA transferase-II; GlcAT-I; GlcAT-II; GlcNAc; GlcNAc transferase; GlcNAcT; Glycosaminoglycan; Glycosyltransferase; HA; HNK-1; HS; HSV; HYAL; N-acetylgalactosamine; N-acetylglucosamine; PG; Proteoglycan; Ser; Sulfotransferase; TM; UST; Xyl; XylT; chondroitin; chondroitin 4-O-sulfotransferase; chondroitin 6-O-sulfotransferase; chondroitin GalNAc transferase; chondroitin polymerizing factor; chondroitin sulfate; chondroitin synthase; chondroitinase ABC; dermatan 4-O-sulfotransferase; dermatan sulfate; exostosin; family with sequence similarity; galactose; glucuronic acid; glycosaminoglycan; heparan sulfate; herpes simplex virus; human natural killer-1; hyaluronan; mammalian hyaluronidase; proteoglycan; serine; thrombomodulin; uronyl 2-O-sulfotransferase; xylose; xylosyltransferase; β1,3-galactosyltransferase-II; β1,3-glucuronyltransferase-I; β1,4-galactosyltransferase-I.