Technologies to Elucidate Functions of Glycans

  • Koichi FurukawaEmail author
  • Yuhsuke Ohmi
  • Yuji Kondo
  • Yuki Ohkawa
  • Orie Tajima
  • Keiko Furukawa
  • Koichi HonkeEmail author
  • Jin-ichi InokuchiEmail author
  • Jianguo GuEmail author
  • Kenji KadomatsuEmail author
  • Satomi Nadanaka
  • Hiroshi KitagawaEmail author
  • Shoko NishiharaEmail author
  • Kazuya NomuraEmail author
  • Shogo OkaEmail author
  • Makoto ItoEmail author
  • Ken KitajimaEmail author
  • Shunji NatsukaEmail author
  • Motoi KanagawaEmail author
  • Takeshi IshimizuEmail author
  • Kazuhito FujiyamaEmail author
  • Yasunori ChibaEmail author
  • Hiroyuki OsadaEmail author


Knockout, Transgenic, Neurodegeneration, Maintenance of homeostasis, Lipid rafts


References for Section 4.1

  1. 1.
    Furukawa K et al (2017) Glycolipids: essential regulator of neuro-inflammation, metabolism and gliomagenesis. Biochim Biophys Acta 1861:2479–2484CrossRefGoogle Scholar
  2. 2.
    Ji S et al (2016) Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice. Biochem Biophys Res Commun 479:453–460CrossRefGoogle Scholar
  3. 3.
    Furukawa K et al (2016) Roles of glycosphingolipids in the regulation of the membrane organization and cell signaling in lipid rafts. In: Lipid/rafts. Nova Science Publishers, London, pp 129–146Google Scholar
  4. 4.
    Furukawa K et al (2014) Glycosphingolipids in the regulation of the nervous system. Adv Neurobiol 9:307–320CrossRefGoogle Scholar
  5. 5.
    Ohmi Y et al (2014) Ganglioside deficiency causes inflammation and neurodegeneration via the activation of complement system in the spinal cord. J Neuroinflammation 11:61CrossRefGoogle Scholar

References for Section 4.2

  1. 6.
    Lowe JB, Marth JD (2003) A genetic approach to mammalian glycan function. Annu Rev Biochem 72:643–691CrossRefGoogle Scholar
  2. 7.
    Furukawa K et al (2007) Knockout mice and glycolipids. In: Kamerling JP et al (eds) Comprehensive glycoscience from chemistry to systems biology, vol 4. Elsevier, Oxford, pp 149–157CrossRefGoogle Scholar
  3. 8.
    Honke K, Taniguchi N (2009) Animal models to delineate glycan functionality. In: Gabius H-J (ed) The sugar code, fundamentals of glycosciences. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp 385–401Google Scholar
  4. 9.
    Inokuchi J (2011) Physiopathological function of hematoside (GM3 ganglioside). Proc Jpn Acad Ser B Phys Biol Sci 87:179–198CrossRefGoogle Scholar
  5. 10.
    Furukawa K et al (2017) Glycolipids: essential regulator of neuro-inflammation, metabolism and gliomagenesis. Biochim Biophys Acta 1861:2479–2484CrossRefGoogle Scholar

References for Section 4.3

  1. 11.
    Laura M, Proia RL (2014) Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function. Glycoconj J 31:613–622CrossRefGoogle Scholar
  2. 12.
    Simpson MA et al (2004) Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase. Nat Genet 36:1225–1229CrossRefGoogle Scholar
  3. 13.
    Boukhris A et al (2013) Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. Am J Hum Genet 93:118–123CrossRefGoogle Scholar
  4. 14.
    Yoshikawa M et al (2015) Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells. Hum Mol Genet 24:2796–2807CrossRefGoogle Scholar
  5. 15.
    Nagafuku M et al (2015) Control of homeostatic and pathogenic balance in adipose tissue by ganglioside GM3. Glycobiology 25:303–318CrossRefGoogle Scholar

References for Section 4.4

  1. 16.
    Haltiwanger RS, Lowe JB (2004) Role of glycosylation in development. Annu Rev Biochem 73:491–537CrossRefGoogle Scholar
  2. 17.
    Apweiler R et al (1999) On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochim Biophys Acta 1473:4–8CrossRefGoogle Scholar
  3. 18.
    Hang Q et al (2016) N-Glycosylation of integrin α5 acts as a switch for EGFR-mediated complex formation of integrin α5β1 to α6β4. Sci Rep 6:33507CrossRefGoogle Scholar
  4. 19.
    Jaeken J, Peanne R (2017) What is new in CDG? J Inherit Metab Dis 40:569–586CrossRefGoogle Scholar

References for Section 4.5

  1. 20.
    Mizumoto S et al (2014) Human genetic disorders and knockout mice deficient in glycosaminoglycan. Biomed Res Int 2014:495764CrossRefGoogle Scholar
  2. 21.
    Kitakaze K et al (2016) Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model. J Clin Invest 126:1691–1703CrossRefGoogle Scholar
  3. 22.
    Ito Z et al (2010) N-acetylglucosamine 6-O-sulfotransferase-1-deficient mice show better functional recovery after spinal cord injury. J Neurosci 30:5937–5947CrossRefGoogle Scholar
  4. 23.
    Coles CH et al (2011) Proteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension. Science 332:484–488CrossRefGoogle Scholar
  5. 24.
    Miyata S et al (2012) Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat Neurosci 15:414–422CrossRefGoogle Scholar

References for Section 4.6

  1. 25.
    Mizumoto S et al (2013) Human genetic disorders caused by mutations in genes encoding biosynthetic enzymes for sulfated glycosaminoglycans. J Biol Chem 288:10953–10961CrossRefGoogle Scholar
  2. 26.
    Inatani M et al (2003) Mammalian brain morphogenesis and midline axon guidance require heparan sulfate. Science 302:1044–1046CrossRefGoogle Scholar
  3. 27.
    Forsberg E, Kjellen L (2001) Heparan sulfate: lessons from knockout mice. J Clin Invest 108:175–180CrossRefGoogle Scholar
  4. 28.
    Irie F et al (2012) Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proc Natl Acad Sci U S A 109:5052–5056CrossRefGoogle Scholar
  5. 29.
    Jones KB et al (2009) A mouse model of osteochondromagenesis from clonal inactivation of Ext1 in chondrocytes. Proc Natl Acad Sci U S A 107:2054–2059CrossRefGoogle Scholar

References for Section 4.7

  1. 30.
    Itoh K et al (2016) Mucin-type core 1 glycans regulate the localization of neuromuscular junctions and establishment of muscle cell architecture in Drosophila. Dev Biol 412: 114–127CrossRefGoogle Scholar
  2. 31.
    Yamamoto-Hino M et al (2015) Phenotype-based clustering of glycosylation-related genes by RNAi-mediated gene silencing. Genes Cells 20: 521–542CrossRefGoogle Scholar
  3. 32.
    Nishihara S (2010) Glycosyltransferases and transporters that contribute to proteoglycan synthesis in Drosophila: identification and functional analyses using the heritable and inducible RNAi system. Methods Enzymol 480: 323–51Google Scholar
  4. 33.
    Yamamoto-Hino M et al (2010) Identification of genes required for neural-specific glycosylation using functional genomics. PLoS Genet 23: e1001254CrossRefGoogle Scholar
  5. 34.
    Ueyama M et al (2010) Increased apoptosis of myoblasts in Drosophila model for the Walker-Warburg syndrome. PLoS One 5: e11557CrossRefGoogle Scholar

References for Section 4.8

  1. 35.
    McGary KL et al (2010) Systematic discovery of nonobvious human disease models through orthologous phenotypes. Proc Natl Acad Sci U S A 107:6544–6549CrossRefGoogle Scholar
  2. 36.
    McWhite CD et al (2015) Applications of comparative evolution to human disease genetics. Curr Opin Genet Dev 35:16–24CrossRefGoogle Scholar
  3. 37.
    Akiyoshi S et al (2015) RNAi screening of human glycogene orthologs in the nematode Caenorhabditis elegans and the construction of the C. elegans glycogene database. Glycobiology 25:8–20CrossRefGoogle Scholar
  4. 38.
    Mizuguchi S et al (2003) Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans. Nature 423:443–448CrossRefGoogle Scholar
  5. 39.
    Dejima K et al (2018) An aneuploidy-free and structurally defined balancer chromosome toolkit for Caenorhabditis elegans. Cell Rep 22:232–241CrossRefGoogle Scholar

References for Section 4.9

  1. 40.
  2. 41.
  3. 42.
    Laughlin ST et al (2008) In vivo imaging of membrane-associated glycans in developing zebrafish. Science 320:664–667CrossRefGoogle Scholar
  4. 43.
    Service RF (2012) Looking for a sugar rush. Science 338:321–323CrossRefGoogle Scholar

References for Section 4.10

  1. 44.
    Liu J et al (2017) CRISPR/Cas9 in zebrafish: an efficient combination for human genetic diseases modeling. Hum Genet 136:1–12CrossRefGoogle Scholar
  2. 45.
    Avsar-Ban E et al (2010) Protein O-mannosylation is necessary for normal embryonic development in zebrafish. Glycobiology 20:1089–1102CrossRefGoogle Scholar
  3. 46.
    Uemura N et al (2015) Viable neuronopathic Gaucher disease model in Medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein. PLoS Genet 11:e1005065CrossRefGoogle Scholar
  4. 47.
    Keatinge M et al (2015) Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. Hum Mol Genet 24:6640–6652CrossRefGoogle Scholar
  5. 48.
    Newman M et al (2014) Using the zebrafish model for Alzheimer’s disease research. Front Genet 5:Article 189PubMedGoogle Scholar

References for Section 4.11

  1. 49.
    Westerfield M (2007) The Zebrafish book, 5th Edition; a guide for the laboratory use of zebrafish (Danio rerio), Eugene, University of Oregon Press. Distributed by the Institute of Neuroscience, University of Oregon, Copyright 1993 by Monte Westerfield, Edition 3; For on-line Edition 4,
  2. 50.
    Kinoshita M et al (2009) Medaka: biology, management, and experimental protocols. Willey-Blackwell, AmesCrossRefGoogle Scholar
  3. 51.
    Tonoyama Y et al (2009) Essential role of β-1,4-galactosyltransferase 2 during medaka (Oryzias latipes) gastrulation. Mech Dev 126:580–594CrossRefGoogle Scholar
  4. 52.
    Avsar-Ban E et al (2010) Protein O-mannosylation is necessary for normal embryonic development in zebrafish. Glycobiology 20:1089–1102CrossRefGoogle Scholar
  5. 53.
    Moore CJ et al (2008) Genes required for functional glycosylation of dystroglycan are conserved in zebrafish. Genomics 92:159–167CrossRefGoogle Scholar

References for Section 4.12

  1. 54.
    Westerfield M (2007) The Zebrafish book, 5th Edition; A guide for the laboratory use of zebrafish (Danio rerio). University of Oregon Press, EugeneGoogle Scholar
  2. 55.
    Hisano Y et al (2015) Precise in-frame integration of exogenous DNA mediated by CRISPR/Cas9 system in zebrafish. Sci Rep 5:8841CrossRefGoogle Scholar
  3. 56.
    Hwang WY et al (2013) Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31:227–229CrossRefGoogle Scholar
  4. 57.
    Ansai S, Kinoshita M (2017) Genome Editing of Medaka. Methods Mol Biol 1630:175–188CrossRefGoogle Scholar
  5. 58.
    Hanzawa K et al (2017) Structures and developmental alterations of N-glycans of zebrafish embryos. Glycobiology 27:228–245Google Scholar

References for Section 4.13

  1. 59.
    Buchanan BB et al (2000) Biochemistry & molecular biology of plants. American Society of Plant Physiologists, RockvilleGoogle Scholar
  2. 60.
    Lombard V et al (2014) The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res 42:D490–D495CrossRefGoogle Scholar
  3. 61.
    Tan HT et al (2016) Emerging technologies for the production of renewable liquid transport fuels from biomass sources enriched in plant cell walls. Front Plant Sci 7:1854PubMedPubMedCentralGoogle Scholar
  4. 62.
    Albersheim P et al (2011) Plant cell walls, Garland ScienceGoogle Scholar
  5. 63.
    Dicker M, Strasser R (2015) Using glyco-engineering to produce therapeutic proteins. Expert Opin Biol Ther 15:1501–1516CrossRefGoogle Scholar

References for Section 4.14

  1. 64.
    Pedersen CT et al (2017) N-glycan maturation mutants in Lotus japonicus for basic and applied glycoprotein research. Plant J 91:394–497CrossRefGoogle Scholar
  2. 65.
    Mercx S et al (2017) Inactivation of the β(1,2)-xylosyltransferase and the α(1,3)-fucosyltransferase genes in Nicotiana tabacum BY-2 cells by a multiplex CRISPR/Cas9 strategy results in glycoproteins without plant-specific glycans. Front Plant Sci 8:403CrossRefGoogle Scholar
  3. 66.
    Limkul J et al (2016) The production of human glucocerebrosidase in glyco-engineered Nicotiana benthamiana plants. Plant Biotechnol J 14:1682–1694CrossRefGoogle Scholar
  4. 67.
    von Schaewen A et al (2015) Arabidopsis thaliana KORRIGAN1 protein: N-glycan modification, localization, and function in cellulose biosynthesis and osmotic stress responses. Plant Signal Behav 10:e1024397Google Scholar

References for Section 4.15

  1. 68.
    Chiba Y et al (1998) Production of human compatible high mannose-type (Man5GlcNAc2) sugar chains in Saccharomyces cerevisiae. J Biol Chem 273:26298–26304CrossRefGoogle Scholar
  2. 69.
    Choi BK et al (2003) Use of combinatorial genetic libraries to humanize N-linked glycosylation in the yeast Pichia pastoris. Proc Natl Acad Sci U S A 100:5022–5027CrossRefGoogle Scholar
  3. 70.
    Kuroda K et al (2008) Efficient antibody production upon suppression of O mannosylation in the yeast Ogataea minuta. Appl Environ Microbiol 74:446–453CrossRefGoogle Scholar
  4. 71.
    Nett JH et al (2005) Cloning and disruption of the Pichia pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and their use as auxotrophic markers. Yeast 22:295–304CrossRefGoogle Scholar
  5. 72.
    Jacobs PP et al (2009) Engineering complex-type N-glycosylation in Pichia pastoris using GlycoSwitch technology. Nat Protoc 4:58–70CrossRefGoogle Scholar

References for Section 4.16

  1. 73.
    Osada H (2010) Introduction of new tools for chemical biology research on microbial metabolites. Biosci Biotechnol Biochem 74:1135–1140CrossRefGoogle Scholar
  2. 74.
    Miyazaki I et al (2010) A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. Nat Chem Biol 6:667–673CrossRefGoogle Scholar
  3. 75.
    Kato N et al (2012) Construction of a microbial natural product library for chemical biology studies. Curr Opin Chem Biol 16:101–108CrossRefGoogle Scholar
  4. 76.
    Kawatani M et al (2015) Identification of matrix metalloproteinase inhibitors by chemical arrays. Biosci Biotechnol Biochem 79:1597–1602CrossRefGoogle Scholar
  5. 77.
    Piotrowski JS et al (2017) Functional annotation of chemical libraries across diverse biologocal processes. Nat Chem Biol 13:982–993. (errata, 13, 1286)CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Chubu UniversityKasugaiJapan
  2. 2.Oklahoma Medical Research FoundationOklahoma CityUSA
  3. 3.Osaka International Cancer InstituteOsakaJapan
  4. 4.Kochi UniversityKochiJapan
  5. 5.Tohoku Medical and Pharmaceutical UniversitySendaiJapan
  6. 6.Nagoya UniversityNagoyaJapan
  7. 7.Kobe Pharmaceutical UniversityKobeJapan
  8. 8.Soka UniversityHachiojiJapan
  9. 9.Kurume UniversityKurumeJapan
  10. 10.Kyoto UniversityKyotoJapan
  11. 11.Kyushu UniversityFukuokaJapan
  12. 12.Niigata UniversityNiigataJapan
  13. 13.Kobe UniversityKobeJapan
  14. 14.Ritsumeikan UniversityKusatsuJapan
  15. 15.Osaka UniversitySuitaJapan
  16. 16.National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  17. 17.RIKENWakoJapan

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