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Functions of Heparan Sulfate Proteoglycans in Morphogenesis

  • Hiroko Habuchi
  • Koji Kimata

Abstract

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.

Keywords

Heparan Sulfate Retinal Ganglion Cell Heparan Sulfate Proteoglycan Renal Agenesis Hereditary Multiple Exostosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • Hiroko Habuchi
    • 1
  • Koji Kimata
    • 1
  1. 1.Institute for Molecular Science of MedicineAichi Medical UniversityNagakute, AichiJapan

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