Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
ISSN-L : 0915-7352
Volume 32 , Issue 190
Showing 1-14 articles out of 14 articles from the selected issue
MINIREVIEW
  • Masamichi Nagae
    2020 Volume 32 Issue 190 Pages E183-E187
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS

    Substances released from pathogens and damaged cells are specifically captured by various pattern recognition receptors in the host immune system. Of these it is the C-type lectin receptors (CLRs) whose function it is to recognize various types of ligands including glycans, glycolipids, lipids and proteins via small C-type lectin domains and to then transduce signals across the membrane. The released glycolipids are specifically recognized by various CLRs involved in the immune response. In this review, I briefly introduce structural aspects of the glycolipid recognition mechanisms of three CLRs involved in mycobacterial infection. These are Mincle, DCAR and Dectin-2. Mincle binds trehalose dimycolate and glycerol monomycolate which are cell wall components of mycobacteria, but it also binds to various (glyco)lipids such as β-glucosylceramide and cholesterol crystals derived from damaged cells. 3D structural analysis has revealed that Mincle has a sugar binding site that recognizes the trehalose disaccharide unit and a hydrophobic groove that accommodates the acyl chains. DCAR interacts with another mycobacterial glycolipid, phosphatidyl-myo-inositol mannoside. DCAR also accepts acyl chains via a hydrophobic groove, but it is situated in a very different position from that in Mincle. Dectin-2 binds mannose-capped lipoarabinomannan (Man-LAM), a glycolipid of pathogenic mycobacteria, via only the disaccharide unit, Manα1-2Man, and not the lipid moiety.

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  • Guoyu Liu, Xiao-Dong Gao, Hideki Nakanishi
    2020 Volume 32 Issue 190 Pages E189-E193
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS
    Supplementary material

    When diploid cells of the budding yeast Saccharomyces cerevisiae are incubated under starvation conditions, they differentiate into a dormant and stress-resistant form of haploid cells termed spores. Spores have a cell wall (spore wall) which is more complex than that of vegetative cells. The spore wall is composed of the following layers, from inside to outside: mannan, glucan, chitosan, and dityrosine. While the inner two layers contain shared components between the vegetative cell wall and spore wall, chitosan and dityrosine are unique components of the spore wall. The outer two layers are dispensable for the viability of spores. However, the unique features of these layers endow spores with distinct properties, such as stress resistance. Some of these properties allow spores to be used for beneficial purposes. For example, removal of the dityrosine layer by genetic manipulation leads to exposure of the chitosan layer on the spore surface; such mutant spores can be used as chitosan particles. Furthermore, spores can retain soluble secretory proteins in the spore wall because the dityrosine layer works as a diffusion barrier. Thus, if secretory forms of enzymes are expressed in sporulating cells, the enzymes are entrapped in the spore wall. Spores containing enzymes in the spore wall can be used as enzyme capsules.

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  • Rieko Imae, Naoyuki Kuwabara, Hiroshi Manya, Ryuichi Kato, Tamao Endo
    2020 Volume 32 Issue 190 Pages E195-E200
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS

    We recently revealed that the muscular dystrophy-related O-mannosyl glycan of α-dystroglycan contains a tandem structure consisting of ribitol phosphate, a newly identified glycan constituent in mammals. This unique structure is formed by the ribitol phosphate transferases FKTN and FKRP. However, the synthetic mechanisms, in particular, the substrate recognition mechanism and catalytic machinery of these enzymes, are unknown. This review article initially outlines the synthetic mechanisms of O-mannosyl glycan of α-dystroglycan, illustrates the results of our recent structure-function analysis of FKRP, and finally introduces the latest findings regarding the mechanisms by which a ribitol phosphate is transferred to the glycan.

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GLYCODEBUT
  • Kazuki Miura, Wataru Hakamata
    2020 Volume 32 Issue 190 Pages E201-E204
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS

    Glycosylation is performed by various glycosidases and glycosyltransferases. Glycan formation and degradation by these enzymes is crucial for various physiological events in cells. Recently, functional analysis of glycan-processing enzymes has actively been performed, and the enzymes are focused on novel drug targets. However, previously reported inhibitors for the glycan-processing enzymes have encountered major problems. Additionally, screening systems for the inhibitors of glycan-processing enzymes are lacking. Accordingly, we are developing cell-based fluorescence imaging systems for glycan-processing glycosidases and screening of their novel inhibitors. In this paper, we introduce the development of a quinone methide cleavage (QMC) fluorescent substrate platform for the glycan-processing glycosidase and the discovery of novel glycosidase inhibitors using these platform-based fluorescent substrates.

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GLYCOREVIEW
  • Yusuke Mii
    2020 Volume 32 Issue 190 Pages E205-E211
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS OPEN ACCESS

    As a family of secreted signaling proteins, Wnt contributes to carcinogenesis, stem cell regulation, and various developmental processes in metazoans. Although Wnt has been considered as a morphogen that provides positional information via its concentration gradient, mechanisms by which Wnt proteins disperse in tissues are not fully understood. Heparan sulfate proteoglycans (HSPGs) are involved in distribution and signaling of secreted signaling proteins, including Wnt. Recently we found that HSPGs in Xenopus embryos and HeLa cells form clusters having different degrees of N-sulfation, which we refer to as “HS clusters.” HS clusters are generated from glypicans and modified by N-deacetylase/N-sulfotransferase in Xenopus embryos. They can be classified into N-acetyl-rich and N-sulfo-rich clusters. Importantly, N-sulfo-rich HS clusters may function as scaffolds for endogenous Wnt8, required for both its distribution and signaling. In this review, biological roles of Wnt signaling in embryogenesis and regulation of Wnt distribution and signaling by HSPGs are introduced together with our discovery of HS clusters.

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GLYCOTOPIC
MINIREVIEW (Jpn. Ed.)
  • Masamichi Nagae
    2020 Volume 32 Issue 190 Pages J159-J163
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS

    Substances released from pathogens and damaged cells are specifically captured by various pattern recognition receptors in the host immune system. Of these it is the C-type lectin receptors (CLRs) whose function it is to recognize various types of ligands including glycans, glycolipids, lipids and proteins via small C-type lectin domains and to then transduce signals across the membrane. The released glycolipids are specifically recognized by various CLRs involved in the immune response. In this review, I briefly introduce structural aspects of the glycolipid recognition mechanisms of three CLRs involved in mycobacterial infection. These are Mincle, DCAR and Dectin-2. Mincle binds trehalose dimycolate and glycerol monomycolate which are cell wall components of mycobacteria, but it also binds to various (glyco)lipids such as β-glucosylceramide and cholesterol crystals derived from damaged cells. 3D structural analysis has revealed that Mincle has a sugar binding site that recognizes the trehalose disaccharide unit and a hydrophobic groove that accommodates the acyl chains. DCAR interacts with another mycobacterial glycolipid, phosphatidyl-myo-inositol mannoside. DCAR also accepts acyl chains via a hydrophobic groove, but it is situated in a very different position from that in Mincle. Dectin-2 binds mannose-capped lipoarabinomannan (Man-LAM), a glycolipid of pathogenic mycobacteria, via only the disaccharide unit, Manα1-2Man, and not the lipid moiety.

    Download PDF (3975K)
  • Guoyu Liu, Xiao-Dong Gao, Hideki Nakanishi
    2020 Volume 32 Issue 190 Pages J165-J169
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS
    Supplementary material

    When diploid cells of the budding yeast Saccharomyces cerevisiae are incubated under starvation conditions, they differentiate into a dormant and stress-resistant form of haploid cells termed spores. Spores have a cell wall (spore wall) which is more complex than that of vegetative cells. The spore wall is composed of the following layers, from inside to outside: mannan, glucan, chitosan, and dityrosine. While the inner two layers contain shared components between the vegetative cell wall and spore wall, chitosan and dityrosine are unique components of the spore wall. The outer two layers are dispensable for the viability of spores. However, the unique features of these layers endow spores with distinct properties, such as stress resistance. Some of these properties allow spores to be used for beneficial purposes. For example, removal of the dityrosine layer by genetic manipulation leads to exposure of the chitosan layer on the spore surface; such mutant spores can be used as chitosan particles. Furthermore, spores can retain soluble secretory proteins in the spore wall because the dityrosine layer works as a diffusion barrier. Thus, if secretory forms of enzymes are expressed in sporulating cells, the enzymes are entrapped in the spore wall. Spores containing enzymes in the spore wall can be used as enzyme capsules.

    Download PDF (1535K)
  • Rieko Imae, Naoyuki Kuwabara, Hiroshi Manya, Ryuichi Kato, Tamao Endo
    2020 Volume 32 Issue 190 Pages J171-J176
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS

    We recently revealed that the muscular dystrophy-related O-mannosyl glycan of α-dystroglycan contains a tandem structure consisting of ribitol phosphate, a newly identified glycan constituent in mammals. This unique structure is formed by the ribitol phosphate transferases FKTN and FKRP. However, the synthetic mechanisms, in particular, the substrate recognition mechanism and catalytic machinery of these enzymes, are unknown. This review article initially outlines the synthetic mechanisms of O-mannosyl glycan of α-dystroglycan, illustrates the results of our recent structure-function analysis of FKRP, and finally introduces the latest findings regarding the mechanisms by which a ribitol phosphate is transferred to the glycan.

    Download PDF (3757K)
GLYCODEBUT (Jpn. Ed.)
  • Kazuki Miura, Wataru Hakamata
    2020 Volume 32 Issue 190 Pages J177-J180
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS RESTRICTED ACCESS

    Glycosylation is performed by various glycosidases and glycosyltransferases. Glycan formation and degradation by these enzymes is crucial for various physiological events in cells. Recently, functional analysis of glycan-processing enzymes has actively been performed, and the enzymes are focused on novel drug targets. However, previously reported inhibitors for the glycan-processing enzymes have encountered major problems. Additionally, screening systems for the inhibitors of glycan-processing enzymes are lacking. Accordingly, we are developing cell-based fluorescence imaging systems for glycan-processing glycosidases and screening of their novel inhibitors. In this paper, we introduce the development of a quinone methide cleavage (QMC) fluorescent substrate platform for the glycan-processing glycosidase and the discovery of novel glycosidase inhibitors using these platform-based fluorescent substrates.

    Download PDF (3236K)
GLYCOREVIEW (Jpn. Ed.)
  • Yusuke Mii
    2020 Volume 32 Issue 190 Pages J181-J187
    Published: November 25, 2020
    Released: November 25, 2020
    JOURNALS OPEN ACCESS

    As a family of secreted signaling proteins, Wnt contributes to carcinogenesis, stem cell regulation, and various developmental processes in metazoans. Although Wnt has been considered as a morphogen that provides positional information via its concentration gradient, mechanisms by which Wnt proteins disperse in tissues are not fully understood. Heparan sulfate proteoglycans (HSPGs) are involved in distribution and signaling of secreted signaling proteins, including Wnt. Recently we found that HSPGs in Xenopus embryos and HeLa cells form clusters having different degrees of N-sulfation, which we refer to as “HS clusters.” HS clusters are generated from glypicans and modified by N-deacetylase/N-sulfotransferase in Xenopus embryos. They can be classified into N-acetyl-rich and N-sulfo-rich clusters. Importantly, N-sulfo-rich HS clusters may function as scaffolds for endogenous Wnt8, required for both its distribution and signaling. In this review, biological roles of Wnt signaling in embryogenesis and regulation of Wnt distribution and signaling by HSPGs are introduced together with our discovery of HS clusters.

    Download PDF (1899K)
GLYCOTOPIC (Jpn. Ed.)
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