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The Department of Biomedicine

BBB seminar: Ulf Lindahl

The light and dark sides of heparan sulfate

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Ulf Lindahl
Department of Medical Biochemistry and Microbiology, University of Uppsala, Sweden

The polysaccharide, heparan sulfate (HS) is composed of alternating units of hexuronic acid and glucosamine, and these sugar residues are variously sulfate-substituted at different positions. Proteoglycans carrying HS chains are ubiquitously expressed at cell surfaces and in the extracellular matrix. The structures of these chains are highly variable, yet under strict biosynthetic control. Due to their high negative charge, HS chains interact with a variety of proteins, including growth factors/morphogens and their receptors, chemokines, and extracellular-matrix proteins. These largely ionic interactions serve to regulate key events in embryonic development and in homeostasis. Questions regarding the degree of specificity in HS-protein interactions currently attract much interest.

HS proteoglycans have recently been implicated in several patho-physiological processes. HS-dependent growth factors thus promote tumor-induced angiogenesis. Interactions between viral capsid proteins and HS chains at cell surfaces facilitate viral invasion of cells. Finally, virtually all proteins known to aggregate into amyloid deposits bind HS, as observed in Alzheimer's disease, type 2 diabetes, AA amyloidosis and other amyloid diseases.

Host: Marion Kusche-Gullberg, Department of Biomedicine