Lena Kjellén research group

Cellular design of heparan sulfate

Heparan sulfate structure varies greatly during embryonic development and differs also when heparan sulfate isolated from different tissues and cell types of an adult animal are compared. Biosynthesis takes place in the Golgi compartment and relies on the action of a multitude of enzymes. Our main goals are to find out how the cell decides on a particular heparan sulfate design and to characterize the molecular machinery responsible for its biosynthesis. Our model systems are mouse and zebrafish where we study study biological effects of mutations in biosynthesis enzymes. Embryonic stem cells and embryonic fibroblasts derived from mutant mice as well as mammalian cell-lines overexpressing or lacking selected biosynthesis enzymes are important tools. A sensitive method to determine glycosaminoglycan concentration and structure is available in the lab, enabling analysis of cultured cells as well as small tissue samples. Our focus has been on the biosynthesis enzyme glucosaminyl N-deacetylase/N-sulfotransferase, NDST, which has a key role in heparan sulfate 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.

Sulfation, obviously important in heparan sulfate biosynthesis, also regulates protein and steroid hormone action. New projects in the lab include characterization of sulfate metabolism in zebrafish and in prostate cancer.

Employees (faculty, staff and other members)

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