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Divergent effects of heparan sulfate/heparin biosynthesis enzymes N-deacetylase/N-sulfotransferase 1 and 2 on Mast cell development
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Deficiency of the heparan sulfate (HS) biosynthesis enzyme N-deacetylase/N-sulfotransferase 1 (NDST1) in mice causes severely disturbed HS biosynthesis in all organs, while lack of NDST2 only affects heparin biosynthesis in mast cells (MCs). To investigate the individual and combined roles of NDST1 and NDST2 during MC development, cultured terminally differentiated MCs from adult mice, in vitro differentiated MCs derived from mouse embryos and embryonic stem cells, respectively, have been studied. While MC development will not occur in the absence of both NDST1 and NDST2, lack of NDST2 alone results in the generation of defective MCs. Surprisingly, NDST1 deficiency results in the formation of MCs which compared to wild type MCs contain increased levels of proteases specific for the connective tissue type MCs as well as increased amounts and degree of sulfation of heparin. A model of the GAGosome, a tentative Golgi enzyme complex, is used to explain the results.

Keyword [en]
NDST1, NDST2, mast cell, embryonic stem cell, biochemistry
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:uu:diva-123466OAI: oai:DiVA.org:uu-123466DiVA: diva2:314338
Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2015-05-29

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Holmborn, KatarinaDagälv, AndersKjellén, Lena

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Department of Medical Biochemistry and Microbiology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Cell and Molecular Biology

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