Functions of Heparan Sulfate Proteoglycans in Morphogenesis
Heparan sulfate proteoglycans (HSPG) are present ubiquitously on the cell surface and in the extracellular matrix including the basement membranes. There are two families of HSPGs in the cell surface, syndecans and glypicans. HSPGs in the extracellular matrix are mainly perlecan and agrin. These HSPGs bear HS chains through serine residues in the core proteins. Their HS chains interact with divergent bioactive ligands such as growth factors and morphogens (FGFs, Wnts, BMPs, VEGFs, Hh, etc) and their receptors (FGFR, etc), extracellular matrix molecules (collagen, fibronectin, laminin, etc), proteases, etc. Such interactions modulate the activity, distribution, concentration, and stability of ligands. Thereby, HS chain plays important roles in a variety of developmental, morphogenetic and pathogenic processes. The specificities of the interactions between HS and ligands are thought to be due, at least in part, to the structure of HS characterized by the sulfation patterns and the distributions of isomers of hexuronic acid residues, GlcA or IdoA. The fine and divergent structures of HS are generated in the Golgi apparatus through the coordinate actions of HS modification enzymes, namely, N-deacetylase/Nsulfotransferases (NDSTs), C5-epimerase (Hsepi) and 2-O-, 6-O-, and 3-O-sulfotransferases, following the biosynthesis of the HS backbone structure comprising alternating glucuronic acid (GlcA) and N-acetylglucosamine (GlcNAc) residues (Fig. 1) (Habuchi et al. 2004). Further modification of HS occurs at the cell surface by the action of 6-Oendosulfatase. These modification enzymes, with the exception of Hsepi and HS2ST, exist as multiple isoforms that differ in substrate specificity and expression patterns.
KeywordsHeparan Sulfate Retinal Ganglion Cell Heparan Sulfate Proteoglycan Renal Agenesis Hereditary Multiple Exostosis
Unable to display preview. Download preview PDF.
- Kimata K, Habuchi O, Habuchi H, Watanabe H (2008) Knockout mice and proteoglycans. In: Kamerling JP et al (eds) Comprehensive glycoscience 3:159–191Google Scholar
- Toyoda H, Kinoshita-Toyada A, Selleck SB (2000) Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfate in vitro. J Biol Chem 275:2269–2275PubMedCrossRefGoogle Scholar