Heparan sulfate synthesized by mouse embryonic stem cells deficient in NDST1 and NDST2 is 6-O-sulfated but contains no N-sulfate groups
(2004) In Journal of Biological Chemistry 279(41). p.8-42355- Abstract
Heparan sulfate structure differs significantly between various cell types and during different developmental stages. The diversity is created during biosynthesis by sulfotransferases, which add sulfate groups to the growing chain, and a C5-epimerase, which converts selected glucuronic acid residues to iduronic acid. All these modifications are believed to depend on initial glucosamine N-sulfation carried out by the enzyme glucosaminyl N-deacetylase/N-sulfotransferase (NDST). Here we report that heparan sulfate synthesized by mouse embryonic stem cells deficient in NDST1 and NDST2 completely lacks N-sulfation but still contains 6-O-sulfate groups, demonstrating that 6-O-sulfation can occur without prior N-sulfation. Reverse... (More)
Heparan sulfate structure differs significantly between various cell types and during different developmental stages. The diversity is created during biosynthesis by sulfotransferases, which add sulfate groups to the growing chain, and a C5-epimerase, which converts selected glucuronic acid residues to iduronic acid. All these modifications are believed to depend on initial glucosamine N-sulfation carried out by the enzyme glucosaminyl N-deacetylase/N-sulfotransferase (NDST). Here we report that heparan sulfate synthesized by mouse embryonic stem cells deficient in NDST1 and NDST2 completely lacks N-sulfation but still contains 6-O-sulfate groups, demonstrating that 6-O-sulfation can occur without prior N-sulfation. Reverse transcriptase-PCR analysis indicates that all three identified 6-O-sulfotransferases are expressed by the cells, 6-O-sulfotransferase-1 being the dominating form. The 6-O-sulfated polysaccharide lacking N-sulfate groups also contains N-unsubstituted glucosamine units, raising questions about how these units are generated.
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- author
- Holmborn, Katarina ; Ledin, Johan ; Smeds, Emanuel LU ; Eriksson, Inger ; Kusche-Gullberg, Marion and Kjellén, Lena
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amidohydrolases/genetics, Animals, Blastocyst/metabolism, Carbohydrate Epimerases/chemistry, Chromatography, High Pressure Liquid, Chromatography, Ion Exchange, DNA, Complementary/metabolism, Embryo, Mammalian/metabolism, Gene Expression Regulation, Developmental, Genotype, Glucosamine/chemistry, Glucuronic Acid/metabolism, Glycosaminoglycans, Heparitin Sulfate/biosynthesis, Iduronic Acid/metabolism, Mice, Mice, Transgenic, Nitrous Acid/metabolism, Polysaccharides/chemistry, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells/metabolism, Sulfates/chemistry, Sulfotransferases/genetics, Sulfur/metabolism
- in
- Journal of Biological Chemistry
- volume
- 279
- issue
- 41
- pages
- 8 - 42355
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:5644302242
- pmid:15319440
- ISSN
- 0021-9258
- DOI
- 10.1074/jbc.C400373200
- language
- English
- LU publication?
- no
- id
- 323fd7b3-0c38-4833-9557-1c9d44a9ffad
- date added to LUP
- 2021-07-07 16:09:58
- date last changed
- 2024-01-05 13:11:43
@article{323fd7b3-0c38-4833-9557-1c9d44a9ffad,
abstract = {{<p>Heparan sulfate structure differs significantly between various cell types and during different developmental stages. The diversity is created during biosynthesis by sulfotransferases, which add sulfate groups to the growing chain, and a C5-epimerase, which converts selected glucuronic acid residues to iduronic acid. All these modifications are believed to depend on initial glucosamine N-sulfation carried out by the enzyme glucosaminyl N-deacetylase/N-sulfotransferase (NDST). Here we report that heparan sulfate synthesized by mouse embryonic stem cells deficient in NDST1 and NDST2 completely lacks N-sulfation but still contains 6-O-sulfate groups, demonstrating that 6-O-sulfation can occur without prior N-sulfation. Reverse transcriptase-PCR analysis indicates that all three identified 6-O-sulfotransferases are expressed by the cells, 6-O-sulfotransferase-1 being the dominating form. The 6-O-sulfated polysaccharide lacking N-sulfate groups also contains N-unsubstituted glucosamine units, raising questions about how these units are generated.</p>}},
author = {{Holmborn, Katarina and Ledin, Johan and Smeds, Emanuel and Eriksson, Inger and Kusche-Gullberg, Marion and Kjellén, Lena}},
issn = {{0021-9258}},
keywords = {{Amidohydrolases/genetics; Animals; Blastocyst/metabolism; Carbohydrate Epimerases/chemistry; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; DNA, Complementary/metabolism; Embryo, Mammalian/metabolism; Gene Expression Regulation, Developmental; Genotype; Glucosamine/chemistry; Glucuronic Acid/metabolism; Glycosaminoglycans; Heparitin Sulfate/biosynthesis; Iduronic Acid/metabolism; Mice; Mice, Transgenic; Nitrous Acid/metabolism; Polysaccharides/chemistry; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells/metabolism; Sulfates/chemistry; Sulfotransferases/genetics; Sulfur/metabolism}},
language = {{eng}},
number = {{41}},
pages = {{8--42355}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Heparan sulfate synthesized by mouse embryonic stem cells deficient in NDST1 and NDST2 is 6-O-sulfated but contains no N-sulfate groups}},
url = {{http://dx.doi.org/10.1074/jbc.C400373200}},
doi = {{10.1074/jbc.C400373200}},
volume = {{279}},
year = {{2004}},
}