Abstract
Heparan sulfate (HS) is a complex polysaccharide abundantly found in extracellular matrices and cell surfaces. HS participates in major cellular processes, through its ability to bind and modulate a wide array of signaling proteins. HS/ligand interactions involve saccharide domains of specific sulfation pattern. Assembly of such domains is orchestrated by a complex biosynthesis machinery and their structure is further regulated at the cell surface by post-synthetic modifying enzymes. Amongst them, extracellular sulfatases of the Sulf family catalyze the selective removal of 6-O-sulfate groups, which participate in the binding of many proteins. As such, increasing interest arose on the regulation of HS biological properties by the Sulfs. However, studies of the Sulfs have so far been essentially restricted to the fields of development and tumor progression. The aim of this review is to survey recent data of the literature on the still poorly documented role of the Sulfs during inflammation, and to widen the perspectives for the study of this intriguing regulatory mechanism toward new physiopathological processes.
Highlights
Heparan sulfate proteoglycans (HSPGs) are major components of the cell surface, extracellular matrix (ECM) and basement membrane in most animal cells
Despite growing evidence, Sulfs have remained largely unstudied in the context of inflammation
It is first well established that Heparan Sulfate (HS) 6-O-sulfation is a major structural determinant for the interaction with many chemokines, including CXCL12 [78,79,80], CXCL8 [81, 82], CXCL4 [83, 84] and CCL5 [85]
Summary
Heparan sulfate proteoglycans (HSPGs) are major components of the cell surface, extracellular matrix (ECM) and basement membrane in most animal cells. The polymer undergoes a series of modifications, which include the N-deacetylation/N-sulfation of glucosamine to form N-sulfo glucosamine (GlcNS), the C5 epimerization of GlcA into iduronic acid (IdoA), and O-sulfations at positions C2 of IdoA and C6 (more rarely C3) of glucosamine residues. Tight regulation of these modification steps leads to the generation of specialized saccharide regions termed S-domains, exhibiting both remarkable structural diversity and high sulfation content. Heparin has been widely used as a surrogate of HS S-domains for protein interaction studies
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