NDST2 (N-Deacetylase/N-Sulfotransferase-2) Enzyme Regulates Heparan Sulfate Chain Length
| Autor: | Lena Kjellén, Audrey Deligny, Alison V. Nairn, Anders Lundequist, Tabea Dierker, Anders Dagälv, Catherine L.R. Merry, Inger Eriksson, Kelley W. Moremen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Sulfotransferase Transcription Genetic Papers of the Week Perlecan N-Acetylglucosaminyltransferases Polysaccharide Models Biological Biochemistry Gene Expression Regulation Enzymologic Amidohydrolases Mice 03 medical and health sciences chemistry.chemical_compound medicine Animals Humans Molecular Biology Mice Knockout chemistry.chemical_classification biology HEK 293 cells Cell Biology Heparin Heparan sulfate carbohydrates (lipids) HEK293 Cells 030104 developmental biology Enzyme Proteoglycan chemistry biology.protein Heparitin Sulfate Sulfotransferases medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 291:18600-18607 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.744433 |
| Popis: | Analysis of heparan sulfate synthesized by HEK 293 cells overexpressing murine NDST1 and/or NDST2 demonstrated that the amount of heparan sulfate was increased in NDST2- but not in NDST1-overexpressing cells. Altered transcript expression of genes encoding other biosynthetic enzymes or proteoglycan core proteins could not account for the observed changes. However, the role of NDST2 in regulating the amount of heparan sulfate synthesized was confirmed by analyzing heparan sulfate content in tissues isolated from Ndst2(-/-) mice, which contained reduced levels of the polysaccharide. Detailed disaccharide composition analysis showed no major structural difference between heparan sulfate from control and Ndst2(-/-) tissues, with the exception of heparan sulfate from spleen where the relative amount of trisulfated disaccharides was lowered in the absence of NDST2. In vivo transcript expression levels of the heparan sulfate-polymerizing enzymes Ext1 and Ext2 were also largely unaffected by NDST2 levels, pointing to a mode of regulation other than increased gene transcription. Size estimation of heparan sulfate polysaccharide chains indicated that increased chain lengths in NDST2-overexpressing cells alone could explain the increased heparan sulfate content. A model is discussed where NDST2-specific substrate modification stimulates elongation resulting in increased heparan sulfate chain length. |
| Databáze: | OpenAIRE |
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