The “in and out” of glucosamine 6-O-sulfation: the 6th sense of heparan sulfate

Abstract

The biological properties of Heparan sulfate (HS) polysaccharides essentially rely on their ability to bind and modulate a multitude of protein ligands. These interactions involve internal oligosaccharide sequences defined by their sulfation patterns. Amongst these, the 6-O-sulfation of HS contributes significantly to the polysaccharide structural diversity and is critically involved in the binding of many proteins. HS 6-O-sulfation is catalyzed by 6-O-sulfotransferases (6OSTs) during biosynthesis, and it is further modified by the post-synthetic action of 6-O-endosulfatases (Sulfs), two enzyme families that remain poorly characterized. The aim of the present review is to summarize the contribution of 6-O-sulfates in HS structure/function relationships and to discuss the present knowledge on the complex mechanisms regulating HS 6-O-sulfation.

Sulfatase 2 promotes generation of a spinal cord astrocyte subtype that stands out through the expression of Olig2

“…How Sulf2 participates in the control of Olig2+ AP generation remains to be established. Sulf2, together with Sulf1, are recognized as critical regulators of heparan sulfate (HS) activities through their ability to catalyze specific 6‐O‐desulfation of the polysaccharide (El Masri et al, ). HS, found at the cell surface and in the extracellular matrix, interact with many signaling cues and a major determinant of specificity and affinity of HS‐ligand interactions is 6‐O‐sulfation.…”

Bringing Heparan Sulfate Glycomics Together with Proteomics for the Design of Novel Therapeutics: A Historical Perspective

“…Some protein activity does not seem to require specific saccharide sequences . However, some do, even requiring the rarer 3‐ O ‐sulfate group, although the majority appear to use N ‐ and 2‐ O ‐sulfates . The most abundant disaccharide unit in heparin consists of a 2S iduronate linked to an N ‐ and 6‐ O ‐sulfated glucosamine.…”

“…[31] However, some do, even requiring the rarer 3-O-sulfate group, although the majority appear to use Nand 2-O-sulfates. [32] The most abundant disaccharide unit in heparin consists of a 2S iduronate linked to an Nand 6-O-sulfated glucosamine. For the biochemist, the inherent "stickiness" of HS makes the determination of its essentialness a fraught process.…”

Identification of a Sulf2-dependant astrocyte subtype that stands out through the expression of Olig2 in the ventral spinal cord

“…How Sulf2 controls production of this AP subtype remains to be determined. Sulf2 is recognized as a critical regulator of signalling cues important in development, including FGFs, Wnt and BMPs (El Masri et al, 2017). Through its ability to catalyze specific 6-O-desulfation on HS chains, Sulf2 modulates signalling activities in many different ways, regulating either ligand secretion, processing and access to receptors (Rosen and Lemjabbar-Alaoui, 2010).…”

“…Sulf1, by eliminating 6O sulfate groups on HS chains, locally lowers Shh/HSPG interaction and thereby promotes Shh release at the right time to trigger OPC specification from Olig2-expressing pMN cells (Touahri et al, 2012;Al Oustah et al, 2014). Jiang and collaborators (2017) more recently reported that Sulf2, the second member of the Sulf protein family (El Masri et al, 2017), plays a similar role as Sulf1 in triggering the MN to OPC fate change. In the present work, we also investigated the function of Sulf2 in the control of gliogenesis and came to the different conclusion that Sulf2 is dispensable for OPC production.…”