Handbook of Glycosyltransferases and Related Genes pp 1105-1112 | Cite as
N-Deacetylase/N-Sulfotransferase (Heparan Glucosaminyl) 2 (NDST2)
Heparan sulfate (HS) proteoglycans are present at cell surfaces and in the extracellular matrix with important functions both during embryonic development and in normal physiology (Bishop et al. 2007; Bülow and Hobert 2006). They participate in the generation and maintenance of morphogen gradients and act as coreceptors for growth factors and cytokines. Heparin is a highly sulfated variant of HS present in the granules of connective tissue-type mast cells. The mast cell proteoglycans have important roles in the storage of bioactive monoamines as well as mast cell-specific proteases (Rönnberg et al. 2012). Both heparin and HS exert their functions through interactions with proteins, where the sulfation pattern of the polysaccharides determines the nature of the interaction (Lindahl and Li 2009). HS and heparin chains attached to proteoglycan core proteins are synthesized in the Golgi compartment of cells, where modification (sulfation and epimerization) occurs concomitantly with polymerization (Carlsson and Kjellen 2012; Esko and Lindahl 2001). The unmodified polysaccharide consists of N-acetylglucosamine (GlcNAc) residues in alternating sequence with glucuronic acid (GlcA). The first modification is catalyzed by a bifunctional enzyme, glucosaminyl N-deacetylase/N-sulfotransferase (NDST), which replaces acetyl groups in GlcNAc residues with sulfate groups. After N-sulfation, further modifications involving epimerization of glucuronic acid to iduronic acid as well as O-sulfation at different positions take place. The NDST enzymes have a key role in designing the modification patterns, since the enzymes carrying out both epimerization and O-sulfation act predominantly in N-sulfated regions of the polysaccharide. Four mammalian NDST isoforms have been identified, while single orthologs are present in Drosophila melanogaster and Caenorhabditis elegans.
KeywordsMast Cell Heparan Sulfate Glucuronic Acid GlcNAc Residue Morphogen Gradient
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