The Department of Biomedicine

BBB seminar: Lena Kjellén

Heparan sulfate biosynthesis - Clues from knockout mice

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Lena Kjellén
Department of Medical Biochemistry and Microbiology, The Biomedical Center, University of Uppsala, Sweden

Heparan sulfate (HS) proteoglycans on cell surfaces or in basement membranes interact with a large number of physiologically important macromolecules, thereby influencing biological processes. This is of particular importance during embryonic development when HS is required for establishing and maintaining morphogen/cytokine gradients. The HS polysaccharide chains of the proteoglycans, covalently attached to different core proteins, carry negatively charged sulfate groups. The positioning of these sulfate groups contributes to the specificity of the interactions. Our focus has been on the enzyme glucosaminyl N-deacetylase/N-sulfotransferase, NDST, which has a key role in HS design during biosynthesis in the Golgi compartment. NDST removes acetyl groups from glucosamine residues and replaces them with sulfate groups. These N-sulfate groups are important for further modifications including, O-sulfation in various positions and epimerization of glucuronic acid to iduronic acid. Four NDST isoforms, transcribed from four genes, have been identified. Our current projects include studies on:
· NDST deficient mice
· HS structure in small tissue samples
· Organization of the HS biosynthesis enzymes in the Golgi compartment
· NDST catalytical properties and maturation
In my presentation these areas will be discussed in relation to results obtained by other groups in the field of HS biosynthesis and biological functions.

Host: Marion Kusche-Gullberg, Department of Biomedicine

Prof. Lena Kjellén has a PhD from Uppsala University in medical chemistry. Her area of research is heparan sulfate proteoglycans where she has studied both their biosynthesis and more functional aspects. During recent years she has generated and utilised mice deficient in heparan sulfate biosynthesis enzymes for her studies. Since 2001 she is professor in medical glycobiology at Uppsala University where she moved from the Swedish University of Agricultural Sciences.