Heparan sulfate

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB (Granzyme B), and tumour metastasis. HS has been shown to serve as cellular receptor for a number of viruses including the respiratory syncytial virus (Hallak et al. 2000)

The major cell membrane HSPGs are the transmembrane syndecans and the glycosylphosphatidylinositol (GPI) anchored glypicans. Other minor forms of membrane HSPG include betaglycan and the V-3 isoform of CD44 present on keratinocytes and activated monocytes.

In the extracellular matrix, especially basement membranes, the multi-domain perlecan, agrin and collagen XVIII core proteins are the main HS-bearing species.

HSPGs have been implicated in the progression of neurodegenerative diseases. Tau fibrils bind to cell surface HSPGs in a similar manner to prions, triggering intracellular fibril aggregation, suggesting a unifying mechanism for tauopathies and synucleopathies, and potential drug targets.

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