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Heparan sulfate biosynthesis in zebrafish: Five NDST genes with distinct expression patterns during embryonic 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.
(English)Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-97474OAI: oai:DiVA.org:uu-97474DiVA: diva2:172439
Available from: 2008-09-05 Created: 2008-09-05 Last updated: 2011-06-28Bibliographically approved
In thesis
1. Cellular design of heparan sulfate: The NDST enzymes and their regulation
Open this publication in new window or tab >>Cellular design of heparan sulfate: The NDST enzymes and their regulation
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heparan sulfate proteoglycans are proteins with long, unbranched heparan sulfate (HS) polysaccharide chains attached to them. They are found on cell surfaces and in basement membranes where they exert their action by interacting with a wide range of enzymes and signaling molecules and are thereby involved in a range of various processes both during embryonic development and in adult physiology.

A great part of the biological functionality of proteoglycans can be directly related to the polysaccharide part. HS chains display very variable sulfation patterns where highly sulfated regions are responsible for a large part of the biological activity. The biosynthesis of HS is a complex process in which a number of enzymes are involved. Better comprehension of how this process is regulated could reveal clues to how formation of HS sulfation patterns occurs, and thereby how HS functionality is controlled.

This thesis is focusing on regulation of one of the enzymes responsible for HS sulfation, glucosaminyl N-deacetylase/N-sulfotransferase (NDST), in an attempt to understand these mechanisms better. Different aspects of NDST regulation were studied in three projects:

I) “Heparin/heparan sulfate biosynthesis: Processive formation of N-sulfated domains”, where the sulfate donor PAPS is shown to influence the manner in which NDST modifies the substrate, affecting the domain structure of the polysaccharide.

II) “Heparan sulfate biosynthesis: Characterization of an NDST1 splice variant”, where a splice variant of NDST1 which appears to influence NDST1 protein levels and affect HS structure is described.

III) “Heparan sulfate biosynthesis in zebrafish: Five NDST genes with distinct expression patterns during embryonic development”, in which five zebrafish NDSTs were cloned and shown to be expressed in a temporally and spatially regulated manner.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 371
Keyword
heparan sulfate, heparin, proteoglycan, NDST, PAPS, Golgi
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-9231 (URN)978-91-554-7267-2 (ISBN)
Public defence
2008-09-27, B42, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-09-05 Created: 2008-09-05Bibliographically approved

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Kjellén, Lena

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