Directing Neuronal Signaling through Cell-Surface Glycan Engineering

Pulsipher, Abigail; Griffin, Matthew E.; Stone, Shannon E.; Brown, Joshua; Hsieh‐Wilson, Linda C.

doi:10.1021/ja5005174

Cited by 79 publications

(99 citation statements)

References 25 publications

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“…Recent studies have explored the ability to promote neuronal growth through the cell surface presentation of particular sulfated GAGs (Pulsipher et al, 2014). For example, liposomal-mediated delivery of CS-E, but not CS-A or CS-C, polysaccharides to cultured cortical neurons enhanced neurite outgrowth mediated by NGF (Pulsipher et al, 2014). The presentation of CS-E at neuronal cell membranes also stimulated NGF-mediated phosphorylation of Akt.…”

Section: Cspgs As Stimulatory Cues For Neuronal Growthmentioning

confidence: 99%

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Miller

Hsieh‐Wilson

2015

Experimental Neurology

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Chondroitin sulfate proteoglycans (CSPGs) play important roles in the developing and mature nervous system, where they guide axons, maintain stable connections, restrict synaptic plasticity, and prevent axon regeneration following CNS injury. The chondroitin sulfate glycosaminoglycan (CS GAG) chains that decorate CSPGs are essential for their functions. Through these sugar chains, CSPGs are able to bind and regulate the activity of a diverse range of proteins. CSPGs have been found both to promote and inhibit neuronal growth. They can promote neurite outgrowth by binding to various growth factors such as midkine (MK), pleiotrophin (PTN), brain-derived neurotrophic factor (BDNF) and other neurotrophin family members. CSPGs can also inhibit neuronal growth and limit plasticity by interacting with transmembrane receptors such as protein tyrosine phosphatase σ (PTPσ), leukocyte common antigen-related (LAR) receptor protein tyrosine phosphatase, and the Nogo receptors 1 and 3 (NgR1 and NgR3). These CS-protein interactions depend on specific sulfation patterns within the CS GAG chains, and accordingly, particular CS sulfation motifs are upregulated during development, in the mature nervous system, and in response to CNS injury. Thus, spatiotemporal regulation of CS GAG biosynthesis may provide an important mechanism to control the functions of CSPGs and to modulate intracellular signaling pathways. Here, we will discuss these sulfation-dependent processes and highlight how the CS sugars on CSPGs contribute to neuronal growth, axon guidance, and plasticity in the nervous system.

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Section: Cspgs As Stimulatory Cues For Neuronal Growthmentioning

confidence: 99%

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Miller

Hsieh‐Wilson

2015

Experimental Neurology

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“…1–6 It provides a powerful means to elucidate molecular mechanisms by which specific biomolecules perform their functions and may find application in cell therapy by targeting therapeutic cells to specific tissues, 2,7–9 endowing cells with new functions such as recruiting/restoring protein binding or directing cell signaling or stem cell differentiation, 10–13 and altering immune cell responses toward cancerous cells. 14,15 …”

Section: Introductionmentioning

confidence: 99%

Cell-Surface Glyco-Engineering by Exogenous Enzymatic Transfer Using a Bifunctional CMP-Neu5Ac Derivative

Capicciotti¹,

Zong²,

Sheikh³

et al. 2017

J. Am. Chem. Soc.

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Cell-surface engineering strategies that permit long-lived display of well-defined, functionally active molecules are highly attractive for eliciting desired cellular responses and for understanding biological processes. Current methodologies for the exogenous introduction of synthetic biomolecules often result in short-lived presentations, or require genetic manipulation to facilitate membrane attachment. Herein, we report a cell-surface engineering strategy that is based on the use of a CMP-Neu5Ac derivative that is modified at C-5 by a bifunctional entity composed of a complex synthetic heparan sulfate (HS) oligosaccharide and biotin. It is shown that recombinant ST6GAL1 can readily transfer the modified sialic acid to N-glycans of glycoprotein acceptors of living cells resulting in long-lived display. The HS oligosaccharide is functionally active, can restore protein binding, and allows activation of cell signaling events of HS-deficient cells. The cell-surface engineering methodology can easily be adapted to any cell type and is highly amenable to a wide range of complex biomolecules.

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“…A 6- O -sulfated N -acetyl galactosamine (GalNAc6S) containing CS facilitates the infection of B. burgdorferi to cause lyme disease [5] , and 4- O -sulfated N -acetyl galactosamine (GalNAc4S) involves in P. falciparum infection that causes malaria [2a] . A domain containing 4,6 disulfated N -acetyl galactosamine (GalNAc4S6S) residues is proved to be necessary to direct neuronal signaling and inhibit axon growth [3c, 6] . CS in conjunction with glucosamine is prescribed as a treatment for osteoarthritis in Asia and Europe and available as a nutraceutical supplement in US; however, the efficacy remains controversial [7] .…”

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confidence: 99%

Enzymatic Synthesis of Homogeneous Chondroitin Sulfate Oligosaccharides

Liu

2017

Angew Chem Int Ed

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Chondroitin sulfate (CS) is a sulfated polysaccharide that plays essential physiological roles. Here, we report to utilize an enzyme-based method to synthesize a library of CS oligosaccharides consisting of 15 different CS oligosaccharides. The library covers 4-O-sulfated and 6-O-sulfated oligosaccharides with the size ranging from trisaccharide to nonasaccharide. We also demonstrate the synthesis of unnatural 6-O-sulfated CS pentasaccharides containing either a 6-O-sulfo 2-azido galactosamine or a 6-O-sulfo galactosamine residue. The availability of structurally defined CS oligosaccharides offers a novel approach to investigate the biological functions of CS.

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Directing Neuronal Signaling through Cell-Surface Glycan Engineering

Cited by 79 publications

References 25 publications

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Cell-Surface Glyco-Engineering by Exogenous Enzymatic Transfer Using a Bifunctional CMP-Neu5Ac Derivative

Enzymatic Synthesis of Homogeneous Chondroitin Sulfate Oligosaccharides

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