title: Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ.
abstract: Glycosylation is a major protein modification. Although proteins are glycosylated/further modulated by several glycosyltransferases during trafficking from the endoplasmic reticulum to the Golgi apparatus, a certain glycan epitope has only been detected on a limited number of proteins. Of these glycan epitopes, Lewis X is highly expressed in the early stage of a developing brain and plays important roles in cell-cell interaction. The Lewis X epitope is comprised of a trisaccharide (Galβ1-4 (Fucα1-3) GlcNAc), and a key enzyme for the expression of this epitope is α1,3-fucosyltransferase 9. However, the scaffolding glycan structure responsible for the formation of the Lewis X epitope as well as its major carrier protein has not been fully characterized in the nervous system. Here we showed that the Lewis X epitope was mainly expressed on phosphacan/receptor protein tyrosine phosphatase β (RPTPβ) in the developing mouse brain. Expression of the Lewis X epitope was markedly reduced in β1,4-galactosyltransferase 2 (β4GalT2) gene-deficient mice, which indicated that β4GalT2 is a major galactosyltransferase required for the Lewis X epitope. We also showed that the Lewis X epitope almost disappeared due to the knockout of protein O-mannose β1,2-N-acetylglucosaminyltransferase 1, an N-acetylglucosaminyltransferase essential for the synthesis of O-mannosylated glycans, which indicated that the O-mannosylated glycan is responsible for presenting the Lewis X epitope. Since O-mannosylated glycans on phosphacan/RPTPβ could also present human natural killer-1, another glycan epitope specifically expressed in the nervous system, our results revealed the importance of O-mannosylated glycan chains in the presentation of functional glycan epitopes in the brain.
authors.affiliation: Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Yaji
authors.affiliation: Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Manya
authors.affiliation: Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakagawa
authors.affiliation: Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Takematsu
authors.affiliation: Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors.forename: Tamao
authors.initials: T
authors.lastname: Endo
authors.affiliation: Advanced Medical Research Center, Aichi Medical University, Nagakutce, Japan.
authors.forename: Reiji
authors.initials: R
authors.lastname: Kannagi
authors.affiliation: Division of Transgenic Animal Science, Advanced Science Research Center Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshihara
authors.affiliation: Division of Transgenic Animal Science, Advanced Science Research Center.
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.affiliation: Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan shogo@hs.med.kyoto-u.ac.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Oka
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D019556:COS Cells; D002236:Carbohydrate Conformation; D002522:Chlorocebus aethiops; D006031:Glycosylation; D016256:Lewis X Antigen / Q000378:metabolism*; D008351:Mannans / Q000378:metabolism; D008358:Mannose / Q000378:metabolism*; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism*
chemical_list: D016256:Lewis X Antigen; D008351:Mannans; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D008358:Mannose
keywords: Lewis X; O-mannosyl glycan; phosphacan (RPTPβ); poly-N-acetyllactosamine