The aim of the present study was to examine the roles of l-fucose and the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin sulfate/dermatan sulfate (CS/DS) with selected functional molecules in neural tissues. Cell surface glycans and GAGs have evolved over millions of years to become cellular mediators which regulate fundamental aspects of cellular survival. The glycocalyx, which surrounds all cells, actuates responses to growth factors, cytokines and morphogens at the cellular boundary, silencing or activating downstream signaling pathways and gene expression. In this review, we have focused on interactions mediated by l-fucose, KS and CS/DS in the central and peripheral nervous systems. Fucose makes critical contributions in the area of molecular recognition and information transfer in the blood group substances, cytotoxic immunoglobulins, cell fate-mediated Notch-1 interactions, regulation of selectin-mediated neutrophil extravasation in innate immunity and CD-34-mediated new blood vessel development, and the targeting of neuroprogenitor cells to damaged neural tissue. Fucosylated glycoproteins regulate delivery of synaptic neurotransmitters and neural function. Neural KS proteoglycans (PGs) were examined in terms of cellular regulation and their interactive properties with neuroregulatory molecules. The paradoxical properties of CS/DS isomers decorating matrix and transmembrane PGs and the positive and negative regulatory cues they provide to neurons are also discussed.
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Cover Image
Cover Image
Cartoon illustration of the simultaneous binding of PAP (a competitive inhibitor of the physiological enzyme co-factor adeonosine 3′-phosphate 5′-phosphosulfate, PAPS) and a heptapeptide saccharide substrate (sticks), poised for sulfation (dashed line) in the active site of heparan sulfate 2-O-sulfotransferase (PDB ID: 4NDZ). The PAP(S)-binding site and the oligosaccharide-binding sites provide dual opportunities for the screening, identification and rational design of small molecule inhibitors of this enzyme, which include the highly sulfated polyanionic drug suramin and the promiscuous protein kinase inhibitor rottlerin. Rottlerin competes with the PAPS co-factor in sulfotransferases, opening the door for the discovery and optimisation of other kinase inhibitors that inhibit these classes of enzyme, including protein tyrosine sulfotransferases (TPSTs). For further details, see the article by Byrne et al. in this issue (pages 2417–2433) and its companion article on pages 2435–2455. Image kindly provided by Neil Berry and Patrick Eyers.
Glycans and glycosaminoglycans in neurobiology: key regulators of neuronal cell function and fate
Anthony J. Hayes, James Melrose; Glycans and glycosaminoglycans in neurobiology: key regulators of neuronal cell function and fate. Biochem J 16 August 2018; 475 (15): 2511–2545. doi: https://doi.org/10.1042/BCJ20180283
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