Heparan sulfate and development: differential roles of the N-acetylglucosamine N-deacetylase/N-sulfotransferase isozymes.
Heparan sulfates (HSs) are N- and O-sulfated polysaccharide components of proteoglycans, which are important constituents of the cell surface as well as the extracellular matrix. Heparin, with extensive clinical application as an anticoagulant, is a highly sulfated form of HS present within the granules of connective tissue type mast cells. The diverse functions of HS, which include the modulation of growth factor/cytokine activity, interaction with matrix proteins and binding of enzymes to cell surfaces, depend greatly on the presence of specific, high affinity regions on the chains. N-acetylglucosamine N-deacetylase/N-sulfotransferases, NDSTs, are an important group of enzymes in HS biosynthesis, initiating the sulfation of the polysaccharide chains and thus determining the generation of the high affinity sites. Here, we review the role of the four vertebrate NDSTs in HS biosynthesis as well as their regulated expression. The main emphasis is the phenotypes of mice lacking one or more of the NDSTs.
Grobe
Kay
K
Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093-0687, USA. kgrobe@ucsd.edu
Ledin
Johan
J
Ringvall
Maria
M
Holmborn
Katarina
K
Forsberg
Erik
E
Esko
Jeffrey D
JD
Kjellén
Lena
L
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000096:biosynthesis*; D006801:Humans; D007527:Isoenzymes; D051379:Mice; D014176:Protein Biosynthesis; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D000581:Amidohydrolases; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007527:Isoenzymes; D015238:Sulfotransferases; C021350:heparitin sulfotransferase