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

Shohei Yaji, Hiroshi Manya, Naoki Nakagawa, Hiromu Takematsu, Tamao Endo, Reiji Kannagi, Toru Yoshihara, Masahide Asano, Shogo Oka

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)376-385
Number of pages10
JournalGlycobiology
Volume25
Issue number4
DOIs
Publication statusPublished - 01-04-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry

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