Glycomics Approach to Structure-Function Relationships of Glycosaminoglycans

Sasisekharan, Ram; Raman, Rahul; Prabhakar, Vikas

doi:10.1146/annurev.bioeng.8.061505.095745

Cited by 263 publications

(231 citation statements)

References 200 publications

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“…GAGs exert their biological effects by interacting with growth factors or cytokines and their receptors, thereby influencing various signaling pathways (Sasisekharan et al, 2006). CS and DS chains interact with several growth factors or cytokines that regulate maintenance and self-renewal of NSCs (Crespo et al, 2007): deglycosylation of CS-DSPGs by ChaseABC treatment impaired FGF-2-mediated neurosphere formation and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

Bian

Akyüz

Bernreuther

et al. 2011

Journal of Cell Science

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SummaryChondroitin sulfates (CSs) and dermatan sulfates (DSs) are enriched in the microenvironment of neural stem cells (NSCs) during development and in the adult neurogenic niche, and have been implicated in mechanisms governing neural precursor migration, proliferation and differentiation. In contrast to previous studies, in which a chondroitinaseABC-dependent unselective deglycosylation of both CSs and DSs was performed, we used chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1)-and dermatan 4-O-sulfotransferase-1 (Chst14/D4st1)-deficient NSCs specific for CSs and DSs, respectively, to investigate the involvement of specific sulfation profiles of CS and DS chains, and thus the potentially distinct roles of CSs and DSs in NSC biology. In comparison to wild-type controls, deficiency for Chst14 resulted in decreased neurogenesis and diminished proliferation of NSCs accompanied by increased expression of GLAST and decreased expression of Mash-1, and an upregulation of the expression of the receptors for fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF). By contrast, deficiency in Chst11 did not influence NSC proliferation, migration or differentiation. These observations indicate for the first time that CSs and DSs play distinct roles in the self-renewal and differentiation of NSCs.

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Section: Discussionmentioning

confidence: 99%

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

Bian

Akyüz

Bernreuther

et al. 2011

Journal of Cell Science

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“…It is well accepted that the heparin-like segments of heparan sulfate chains are more heavily involved in interactions with target proteins due to their higher degree of sulfation and the conformational flexibility of iduronic residues (60). However, limitations in analytical techniques have made it difficult to isolate the "active" elements of heparan sulfate chain populations (61). In this context, our study could reflect important catalytic roles of heparin-like heparan sulfate regions within the extracellular matrix, especially since heparan sulfate has a similar effect on VEGF binding to fibronectin, albeit at higher concentrations (29).…”

Section: Discussionmentioning

confidence: 99%

A Catalytic Role of Heparin within the Extracellular Matrix

Mitsi

Forsten-Williams

Gopalakrishnan

et al. 2008

Journal of Biological Chemistry

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We investigated the mechanism by which heparin enhances the binding of vascular endothelial growth factor (VEGF) to the extracellular matrix protein fibronectin. In contrast to other systems, where heparin acts as a protein scaffold, we found that heparin functions catalytically to modulate VEGF binding site availability on fibronectin. By measuring the binding of VEGF and heparin to surface-immobilized fibronectin, we show that substoichiometric amounts of heparin exposed cryptic VEGF binding sites within fibronectin that remain available after heparin removal. Measurement of association and dissociation kinetics for heparin binding to fibronectin indicated that the interaction is rapid and transient. We localized the heparin-responsive element to the C-terminal 40-kDa Hep2 domain of fibronectin. A mathematical model of this catalytic process was constructed that supports a mechanism whereby the heparininduced conformational change in fibronectin is accompanied by release of heparin. Experiments with endothelial extracellular matrix suggest that this process may also occur within biological matrices. These results indicate a novel mechanism whereby heparin catalyzes the conversion of fibronectin to an open conformation by transiently interacting with fibronectin and progressively hopping from molecule to molecule.

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“…GAGs are divided into four main categories: hyaluronic acid or hyaluronan (HA), chondroitin/dermatan sulfate, Nacetylheparosan (NAH)/heparan sulfate/heparin, and keratan sulfate, based on their monosaccharide composition and the configuration and position of the glycosidic bonds between these monosaccharides. The specificity of the interactions between GAGs and proteins results from structural diversity of GAGs defined by their size, saccharide composition and sequence, charge density [4,5]. Thus, understanding the structure of a GAG is essential in understanding its activity and biological functions.…”

mentioning

confidence: 99%

Tandem MS can distinguish hyaluronic acid from N-acetylheparosan

Zhang

Xie

Liu³

et al. 2008

J. Am. Soc. Mass Spectrom.

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Isobaric oligosaccharides enzymatically prepared from hyaluronic acid (HA) and N-acetylheparosan (NAH), were distinguished using tandem mass spectrometry. The only difference between the two series of oligosaccharides was the linkage pattern (in HA 1¡3 and in NAH 1¡4) between glucuronic acid and N-acetylglucosamine residues. Tandem mass spectrometry afforded spectra in which glycosidic cleavage fragment ions were observed for both HA and NAH oligosaccharides. Cross-ring cleavage ions 0,2 A n and 0,2 A n -h (n is even number) were observed only in GlcNAc residues of NAH oligosaccharides. One exception was an 0,2 A 2 ion fragment observed for the disaccharide from HA. These cross-ring cleavage fragment ions are useful to definitively distinguish HA and NAH oligosaccharides. -3]. GAGs are divided into four main categories: hyaluronic acid or hyaluronan (HA), chondroitin/dermatan sulfate, Nacetylheparosan (NAH)/heparan sulfate/heparin, and keratan sulfate, based on their monosaccharide composition and the configuration and position of the glycosidic bonds between these monosaccharides. The specificity of the interactions between GAGs and proteins results from structural diversity of GAGs defined by their size, saccharide composition and sequence, charge density [4,5]. Thus, understanding the structure of a GAG is essential in understanding its activity and biological functions. HA and NAH are biosynthesized by both prokaryotic and eukaryotic cells. HA is copolymer linked polymer of ␤-1,4 D-glucuronic acid (GlcA) and ␤-1,3 D-N-acetylglucosamine (GlcNAc) [6]. NAH is a copolymer of ␤-1,4 GlcA and ␣-1,4 GlcNAc and the biosynthetic precursor of the mammalian GAGs, heparin and heparan sulfate [7]. HA can be prepared by bacterial fermentation of Streptococcus zooepidemicus [8], or enzymatically using biosynthetic enzymes prepared from Pasturella multocida [9]. Bacteria use HA as camouflage to enhance their ability to infect higher animals [10]. Similarly, Escherichia coli strain K5 produces capsular polysaccharide comprised of NAH [11]. NAH is also important as it represents a considerable portion of the sequence of mammalian heparan sulfate [12,13]. HA and NAH are the two simplest GAGs since neither has sulfo groups and, thus, consist of only a single sequence (Figure 1). HA and NAH have very similar structures, differing only in the position of their glycosidic linkage between GlcA and GlcNAc. This difference in structure results from very different biosynthesis pathways for HA and NAH [14 -17] and gives each polysaccharide unique biological functions and distinctive structure-activity relationships [18].The oligosaccharides prepared from GAGs by controlled enzymatic depolymerization are often studied to define the minimum structural requirements for biological activity [19,20]. ESI-MS is particularly useful to monitor these GAG-derived oligosaccharides due to its soft ionization [21,22]. LC-ESI-MS, relying on reversedphase ion-pairing (RPIP)-high-performance liquid chromatography (HPLC), has employed volatile ion-pai...

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Glycomics Approach to Structure-Function Relationships of Glycosaminoglycans

Cited by 263 publications

References 200 publications

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

A Catalytic Role of Heparin within the Extracellular Matrix

Tandem MS can distinguish hyaluronic acid from N-acetylheparosan

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