3-O-sulfated heparan sulfate interactors target synaptic adhesion molecules from neonatal mouse brain and inhibit neural activity and synaptogenesis in vitro

Maïza, Auriane; Sidahmed-Adrar, Nazha; Michel, Patrick P.; Carpentier, Gilles; Habert, Damien; Dalle, Carine; Redouane, Walid; Hamza, Magda; Kuppevelt, TH van; Ouidja, Mohand Ouidir; Courty, José; Chantepie, Sandrine; Papy-García, Dulce; Stettler, Olivier

doi:10.1038/s41598-020-76030-4

Cited by 13 publications

(11 citation statements)

References 54 publications

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“…37 The sulfotransferases HS2ST1 and HS3ST2 add sulfates to the 2-O position of iduronic acid and to the 3-O position of the glucosamine and are relevant enzymes to HS final charge density. They are also involved in developmental anomalies 38 and in the regulation of breast cancer stem-cell function. 39 Interestingly, while NDST1 and NDST2 have similar effectiveness in the sulfotransferase and deacetylase activities, NDST4 is more effective in transferring sulfate groups than removing acetyl groups, and NDST3 has the opposite behavior.…”

Section: Heparan Sulfate: Biosynthesis and Biologymentioning

confidence: 99%

Heparan sulfate fine‐tunes stromal‐epithelial communication in the prostate gland

Barbosa

Biancardi

Carvalho

2020

Developmental Dynamics

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Several studies reported the concerted and mutual communication between the prostate epithelium and stroma, which determines the final organ architecture and function, but gets awry in cancer. Deciphering the mechanisms involved in this communication is crucial to find new therapeutic strategies. HS sequesters a number of secreted growth factors and cytokines, controlling their bioavailability to the target cells, suggesting that HS is an important regulator of the extracellular matrix (ECM) and a key player in the cell-cell and cell-microenvironment communication during prostate morphogenesis and physiology. We propose that by controlling HS biosynthesis and sulfation pattern, as well as the cleavage of the HS chain and/or the shedding of proteoglycans, epithelial and stromal cells are able to precisely tune the availability of signaling molecules and modulate ligand-receptor interaction and intracellular signal transduction.

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Section: Heparan Sulfate: Biosynthesis and Biologymentioning

confidence: 99%

Heparan sulfate fine‐tunes stromal‐epithelial communication in the prostate gland

Barbosa

Biancardi

Carvalho

2020

Developmental Dynamics

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“…The role of HSPG sulphation in synaptogenesis has received less attention. However, 3-O-sulphated glypican is necessary for normal synapse formation in the C. elegans mating circuit ( Lazaro-Pena et al, 2018 ), and a blocker of 3-sulphated HS impaired synapse assembly in hippocampal neurons in vitro ( Maiza et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Proteoglycan Sulphation in the Function of the Mature Central Nervous System

Fawcett

Kwok

2022

Front. Integr. Neurosci.

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Chondroitin sulphate and heparan sulphate proteoglycans (CSPGS and HSPGs) are found throughout the central nervous system (CNS). CSPGs are ubiquitous in the diffuse extracellular matrix (ECM) between cells and are a major component of perineuronal nets (PNNs), the condensed ECM present around some neurons. HSPGs are more associated with the surface of neurons and glia, with synapses and in the PNNs. Both CSPGs and HSPGs consist of a protein core to which are attached repeating disaccharide chains modified by sulphation at various positions. The sequence of sulphation gives the chains a unique structure and local charge density. These sulphation codes govern the binding properties and biological effects of the proteoglycans. CSPGs are sulphated along their length, the main forms being 6- and 4-sulphated. In general, the chondroitin 4-sulphates are inhibitory to cell attachment and migration, while chondroitin 6-sulphates are more permissive. HSPGs tend to be sulphated in isolated motifs with un-sulphated regions in between. The sulphation patterns of HS motifs and of CS glycan chains govern their binding to the PTPsigma receptor and binding of many effector molecules to the proteoglycans, such as growth factors, morphogens, and molecules involved in neurodegenerative disease. Sulphation patterns change as a result of injury, inflammation and ageing. For CSPGs, attention has focussed on PNNs and their role in the control of plasticity and memory, and on the soluble CSPGs upregulated in glial scar tissue that can inhibit axon regeneration. HSPGs have key roles in development, regulating cell migration and axon growth. In the adult CNS, they have been associated with tau aggregation and amyloid-beta processing, synaptogenesis, growth factor signalling and as a component of the stem cell niche. These functions of CSPGs and HSPGs are strongly influenced by the pattern of sulphation of the glycan chains, the sulphation code. This review focuses on these sulphation patterns and their effects on the function of the mature CNS.

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“…21 In addition, 3-OST-2 and 3-OST-4 are involved in synaptogenesis in neuronal development 7 through 3-O-sulfated HSs. 7,8 The current method to characterize the structure of HS from biological sources is merely to conduct disaccharide compositional analysis. 22 However, the disacchar-ide analysis method is unsuited to determine the level of 3-Osulfated HS modified by 3-OST-2 and 3-OST-4 isolated from brain tissues because 3-O-sulfated saccharide domains are resistant to the heparin lyases degradation.…”

mentioning

confidence: 99%

“…For example, 3- O -sulfation is key for the anticoagulant activity of heparin. 3- O -Sulfated HS serves as a cell entry receptor for herpes simplex virus to establish infection. , 3- O -Sulfated HS has also been shown to contribute to cancer pathogenesis, neural development, and regulation. − The distinct biological functions observed for 3- O -sulfated HS are due to the unique saccharide sequences around the 3- O -sulfation site …”

mentioning

confidence: 99%

“…In a zebrafish model, the HS modified by 3-OST-2 and 3-OST-4 facilitates neurotropic HSV-1 entry and spreads via binding to HSV-1 envelope glycoprotein D (gD). , Both 3-OST-2 and 3-OST-4 have increased expression in the brains with Alzheimer’s disease (AD) . In addition, 3-OST-2 and 3-OST-4 are involved in synaptogenesis in neuronal development through 3- O -sulfated HSs. , The current method to characterize the structure of HS from biological sources is merely to conduct disaccharide compositional analysis . However, the disaccharide analysis method is unsuited to determine the level of 3- O -sulfated HS modified by 3-OST-2 and 3-OST-4 isolated from brain tissues because 3- O -sulfated saccharide domains are resistant to the heparin lyases degradation .…”

mentioning

confidence: 99%

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Synthesis of 3-O-Sulfated Heparan Sulfate Oligosaccharides Using 3-O-Sulfotransferase Isoform 4

Su²,

et al. 2021

ACS Chem. Biol.

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Heparan sulfate (HS) 3-O-sulfotransferase isoform 4 (3-OST-4) is a specialized carbohydrate sulfotransferase participating in the biosynthesis of heparan sulfate. Here, we report the expression and purification of the recombinant 3-OST-4 enzyme and use it for the synthesis of a library of 3-O-sulfated hexasaccharides and 3-O-sulfated octasaccharides. The unique structural feature of the library is that each oligosaccharide contains a disaccharide domain with a 2-O-sulfated glucuronic acid (GlcA2S) and 3-O-sulfated glucosamine (GlcNS3S). By rearranging the order of the enzymatic modification steps, we demonstrate the synthesis of oligosaccharides with different saccharide sequences. The structural characterization was completed by electrospray ionization mass spectrometry and NMR. These 3-O-sulfated oligosaccharides show weak to very weak anti-Factor Xa activity, a measurement of anticoagulant activity. We discovered that HSoligo 7 (HS oligosaccharide 7), a 3-O-sulfated octasaccharide, binds to high mobility group box 1 protein (HMGB1) and tau protein, both believed to be involved in the process of inflammation. Access to the recombinant 3-OST-4 expands the capability of the chemoenzymatic method to synthesize novel 3-O-sulfated oligosaccharides. The oligosaccharides will become valuable reagents to probe the biological functions of 3-O-sulfated HS and to develop HS-based therapeutic agents.

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3-O-sulfated heparan sulfate interactors target synaptic adhesion molecules from neonatal mouse brain and inhibit neural activity and synaptogenesis in vitro

Cited by 13 publications

References 54 publications

Heparan sulfate fine‐tunes stromal‐epithelial communication in the prostate gland

Heparan sulfate fine‐tunes stromal‐epithelial communication in the prostate gland

Proteoglycan Sulphation in the Function of the Mature Central Nervous System

Synthesis of 3-O-Sulfated Heparan Sulfate Oligosaccharides Using 3-O-Sulfotransferase Isoform 4

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