TY - JOUR
T1 - Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ
AU - Yaji, Shohei
AU - Manya, Hiroshi
AU - Nakagawa, Naoki
AU - Takematsu, Hiromu
AU - Endo, Tamao
AU - Kannagi, Reiji
AU - Yoshihara, Toru
AU - Asano, Masahide
AU - Oka, Shogo
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas (no. 23110006 to S.O. and no. 24110523 to H.M.) from MEXT of Japan, Grants-in-Aid for Scientific Research (B) (no. 26291021 to S.O. and no. 25293016 to T.E.), Scientific Research (C) (no. 24590078 to H.T.) and JSPS Fellows (no. 252038 to N.N.) from the Japan Society for the Promotion of Science, and a Grant-in-Aid for Intramural Research Grant (26-8) for Neurological and Psychiatric Disorders of NCNP (to T.E.).
Publisher Copyright:
© 2014 The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
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U2 - 10.1093/glycob/cwu118
DO - 10.1093/glycob/cwu118
M3 - Article
C2 - 25361541
AN - SCOPUS:84941047569
VL - 25
SP - 376
EP - 385
JO - Glycobiology
JF - Glycobiology
SN - 0959-6658
IS - 4
ER -