Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
Volume 7 , Issue 38
Showing 1-9 articles out of 9 articles from the selected issue
  • J. McLeod Griffiss, [in Japanese], [in Japanese]
    1995 Volume 7 Issue 38 Pages 461-478
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Lipooligosaccharides (LOS) are made by Gram negative bacteria that colonize mucosal surfaces other than those of the gut (1). These surface-exposed outer membrane organelles structurally resemble human cell membrane glycosphingolipids (GSL) more than they do the analogous lipopolysaccharides (LPS) of enteric Gram negative bacteria (1-3).
    One highly conserved LOS has the same lacto-N-neotetraose (LacNAcβ1→3Lac) glycose moiety (2, 4-6) as paragloboside-series GSL (7-9); other LOS glycose structures are shared with those of ganglio-(GalNAcβ1→3Gal-R), globo-(Galα1→4Lac-R, or P-series), and lacto-series (Lac-R) GSL (3, 10). By having the same surface glycose structures as human cells, these organisms can evade immune recognition (11-13).
    LOS biosynthesis is flexible. Lacto-N-neotetraose is formed by the β1→3 linkage of the disaccharide, lactosamine (LacNAc; Galβ1→4GlcNAc), to lactose (Lac; Galβ1→4Glc). The internal, or lactosyl, galactose (Gal) is a “toggle switch”, or biosynthetic decision point: the glycose linked to it determines the structure of the mature LOS. A second Gal residue linked to it α1→4 (Pk globoside) stops further chain elongation, and the LOS terminates with the digalactoside. On the other hand, if glucosamine (GlcNAc) is added β1→3 to the lactosyl Gal, then a second Gal residue is added β1→4 to the GlcNAc residue to form the LacNAc disaccharide of lacto-N-neotetraose.
    The LacNAc terminal Gal is a second biosynthetic decision point: it may be unsubstituted (paraglobosyl) (2), adorned with sialic acid (sialoparaglobosyl) (14, 15), or substituted with galactosamine (GalNAc) in the β configuration (asialo-G3 gangliosyl) (6, 16). Sialylation of their LOS prevents lysis of the organisms by complement (immune lysis) (14, 17), retards their killing by polymorphonuclear leukocytes (PMNs) (18, 19) and enhances their ability to invade endocervical epithelial cells (20). Galactosaminylation provides a terminal GalNAc that binds bactericidal IgM molecules that are ubiquitous in human sera (21, 22). These antibodies initiate immune lysis of organisms that enter the blood stream (11) and thereby restrict colonization to the mucosa.
    Mucosal bacteria can vary LOS biosynthesis so as to express several different glycolipids that each mimic a different human GSL (3). LOS phase variation is quite rapid (10-3) (23, 24). This suggests that it may enable the organisms' to survive in different molecular environments, e. g., the mucosae of venereal consorts of different blood types, or the respiratory mucosa and subarachnoid space of a patient who develops meningitis. LOS phase shifts occur during the development of disease. A shift to Neisseria gonorrhoeae variants that make paraglobosyl, gangliosyl and higher Mr LOSs heralds the onset of symptomatic (? infectious) urethral leukorrhoea during gonococcal infection in men (24). Gonococci also must make paraglobosyl LOS that can be sialylated in order to invade endocervical epithelial cells (20).
    LOS biosynthetic genes currently are being identified. The “gene phase” of LOS biology opens up the possibility of discovering exactly how potentially pathogenic bacteria use their LOS to ensure their survival on various mucosal surfaces to cause disease in humans.
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  • Chi-Hung Siu, [in Japanese]
    1995 Volume 7 Issue 38 Pages 479-493
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    The neural cell adhesion molecule NCAM is a member of the immunoglobulin (Ig)-superfamily of recognition molecules. NCAM is a multidomain molecule which can interact with a variety of ligands. NCAM is also capable of homophilic binding, which plays a crucial role in cell-cell adhesion. Recent studies have led to the identification of the homophilic binding site to a decapeptide sequence (243-KYSFNYDGSE-252) in the third Ig-like domain of chick NCAM. This sequence corresponds to the C' β-strand and the subsequent turn structure in the predicted Ig fold. Mutational analysis indicates that the aromatic residues Tyr-244 and Phe-246, as well as the charged residues Lys-243 and Asp-249, are crucial to NCAM-NCAM binding. Further studies have shown that recombinant Ig-like domain 3 of NCAM can undergo homophilic binding, which isabolished when mutations are introduced into this decapeptide bi nding site. These results are consistent with the model that the NCAM homophilic binding site interacts isologously with the same sequence on apposing molecules. The integrity of its homophilic binding site is an absolute requirement for NCAM localization in intercellular contact regions. NCAM homophilic binding also triggers a signaling pathway that promotes neurite extension from a number of primary neurons. Thus, the NCAM homophilic binding site plays a key role not only in cell-cell contact formation but also in neurite outgrowth.
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  • Frances M. Platt, Terry D. Butters, [in Japanese]
    1995 Volume 7 Issue 38 Pages 495-511
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Glycosphingolipids (GSLs) are ubiquitous components of eukaryotic cell surfaces and contribute to the glycocalyx, along with other cell surface glycoconjugates. They play a role in recognition events and are exploited as receptors by a number of infectious disease agents. Their expression changes with cell transformation and if they are incompletely catabolised pathology results, leading to the GSL lysosomal storage diseases. However, the role(s) played by the majority of GSL species remain obscure. One approach for probing their functions is to study the effects of GSL depletion using specific inhibitors of GSL biosynthesis. Two structurally distinct classes of GSL biosynthesis inhibitors have been characterised to date, ceramide analogues and N-alkylated imino sugars. Both types of compound inhibit the first step in GSL biosynthesis, namely the glucosyltransferase catalysed synthesis of glucosylceramide. This results in the failure to synthesise all glucosylceramide derived GSL species. GSL depletion using these inhibitors is well tolerated in vitro and in vivo and they offer a novel therapeutic strategy for the treatment of the glycosphingolipid storage diseases, and are invaluable reagents for studying GSL functions.
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  • Ralph D. Sanderson, Brian F. Liebersbach, [in Japanese]
    1995 Volume 7 Issue 38 Pages 513-524
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
    Syndecans are cell surface proteoglycans that mediate cell-matrix and cell-cell adhesion and act as co-receptors for some growth factors. Although little is known regarding the role of syndecans in disease, emerging evidence indicates that they play an important role in regulating the behavior of tumor cells. It has been demonstrated that expression of syndecan-l is essential for maintaining epithelial morphology in vitro and that some tumors growing in vivo reduce or lose their expression of syndecan-l during their transformation to a malignant state. In addition, there is now direct evidence that syndecan-l inhibits tumor cell invasion within the extracellular matrix. Human myeloma cells that do not express syndecan-l will readily invade into type I collagen gels. However, following their transfection with a cDNA for syndecan-l, these cells are rendered non-invasive. These studies indicate that expression of syndecan-l supports a non-invasive phenotype and that loss of syndecan-l expression may be necessary prior to the metastasis of some tumors.
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  • Katarzyna Anna Podyma, [in Japanese]
    1995 Volume 7 Issue 38 Pages 525-526
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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  • M. Ishihara
    1995 Volume 7 Issue 38 Pages 527-528
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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  • Tadashi Suzuki
    1995 Volume 7 Issue 38 Pages 529-531
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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  • Haruko Ogawa, Miwa Tanaka
    1995 Volume 7 Issue 38 Pages 533-535
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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  • Jun Hirabayashi
    1995 Volume 7 Issue 38 Pages 537-539
    Published: November 02, 1995
    Released: January 05, 2010
    JOURNALS FREE ACCESS
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