HSPG

Heparan sulfate proteoglycans (HSPGs) are a diverse group of cell-surface and extracellular matrix proteoglycans characterized by one or more covalently attached heparan sulfate glycosaminoglycan chains. The HS chains are long, linear polysaccharides with variable sulfation patterns that confer capacity to bind a wide range of proteins.

Core proteins include families such as syndecans (transmembrane), glypicans (GPI-anchored), and secreted basement membrane proteoglycans like perlecan and agrin. HSPGs are found on nearly all cell types and in basement membranes, where they contribute to tissue architecture, filtration, and signaling.

Biosynthesis occurs in the endoplasmic reticulum and Golgi apparatus, where HS chains are assembled by glycosyltransferases (EXT1/EXT2) and extensively modified by sulfotransferases (NDSTs and 2-O-, 6-O-, 3-O-sulfotransferases) and epimerases to create sulfation patterns that determine protein interactions.

Functions of HSPGs include presenting and stabilizing growth factors, morphogens, and chemokines to their receptors, thereby modulating signaling pathways such as FGF, VEGF, Wnt, and Hedgehog. They participate in cell adhesion, migration, and ECM organization, and they can influence coagulation balance and inflammatory responses.

Clinical and research notes indicate that altered HSPG expression or HS remodeling is linked to development, wound healing, cancer, and genetic disorders. Mutations in EXT1/EXT2 cause multiple hereditary exostoses; enzymes like heparanase remodel HS to affect the tumor microenvironment. HSPGs are targets for therapeutic approaches, including HS mimetics and HS-degrading enzymes.