Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ

• Published in: Glycobiology (Oxford) Vol. 25; no. 4; pp. 376 - 385
• Main Authors: Yaji, Shohei, Manya, Hiroshi, Nakagawa, Naoki, Takematsu, Hiromu, Endo, Tamao, Kannagi, Reiji, Yoshihara, Toru, Asano, Masahide, Oka, Shogo
• Format: Journal Article
• Language: English
• Published: England 01.04.2015
• Subjects: Animals; Biosynthetic Pathways; Brain - embryology; Brain - enzymology; Brain - growth & development; Carbohydrate Conformation; Cercopithecus aethiops; COS Cells; Glycosylation; Lewis X Antigen - metabolism; Mannans - metabolism; Mannose - metabolism; Mice, Knockout; Protein Processing, Post-Translational; Receptor-Like Protein Tyrosine Phosphatases, Class 5 - metabolism; Lewis X; poly-N-acetyllactosamine; O-mannosyl glycan; phosphacan (RPTPβ)
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/cwu118

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.