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Majority of alpha2,6-sialylated glycans in the adult mouse brain exist in O-glycans: SALSA-MS analysis for knockout mice of alpha2,6-sialyltransferase genes.

Authors
  • Ohmi, Yuhsuke1
  • Nishikaze, Takashi2
  • Kitaura, Yoko1
  • Ito, Takako1
  • Yamamoto, Satoko3
  • Sugiyama, Fumihiro4
  • Matsuyama, Makoto5
  • Takahashi, Yoshimasa6
  • Takeda, Akira1
  • Kawahara, Toshio1
  • Okajima, Tetsuya7
  • Furukawa, Keiko3
  • Furukawa, Koichi3, 7
  • 1 Department of Clinical Engineering, Chubu University College of Life and Health Sciences, Kasugai, Aichi 487-8501, Japan. , (Japan)
  • 2 Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, 1, Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto 604-8511, Japan. , (Japan)
  • 3 Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Aichi 487-8501, Japan. , (Japan)
  • 4 Laboratory Animal Resource Center, University of Tsukuba, Tsukuba 305-8575, Japan. , (Japan)
  • 5 Division of Molecular Genetics, Shigei Medical Research Institute, 2117, Yamada, Minami-ku, Okayama 701-0202, Japan. , (Japan)
  • 6 Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. , (Japan)
  • 7 Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-0065, Japan. , (Japan)
Type
Published Article
Journal
Glycobiology
Publisher
Oxford University Press
Publication Date
Jun 03, 2021
Volume
31
Issue
5
Pages
557–570
Identifiers
DOI: 10.1093/glycob/cwaa105
PMID: 33242079
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Sialic acids are unique sugars with negative charge and exert various biological functions such as regulation of immune systems, maintenance of nerve tissues and expression of malignant properties of cancers. Alpha 2,6 sialylated N-glycans, one of representative sialylation forms, are synthesized by St6gal1 or St6gal2 gene products in humans and mice. Previously, it has been reported that St6gal1 gene is ubiquitously expressed in almost all tissues. On the other hand, St6gal2 gene is expressed mainly in the embryonic and perinatal stages of brain tissues. However, roles of St6gal2 gene have not been clarified. Expression profiles of N-glycans with terminal α2,6 sialic acid generated by St6gal gene products in the brain have never been directly studied. Using conventional lectin blotting and novel sialic acid linkage-specific alkylamidationmass spectrometry method (SALSA-MS), we investigated the function and expression of St6gal genes and profiles of their products in the adult mouse brain by establishing KO mice lacking St6gal1 gene, St6gal2 gene, or both of them (double knockout). Consequently, α2,6-sialylated N-glycans were scarcely detected in adult mouse brain tissues, and a majority of α2,6-sialylated glycans found in the mouse brain were O-linked glycans. The majority of these α2,6-sialylated O-glycans were shown to be disialyl-T antigen and sialyl-(6)T antigen by mass spectrometry analysis. Moreover, it was revealed that a few α2,6-sialylated N-glycans were produced by the action of St6gal1 gene, despite both St6gal1 and St6gal2 genes being expressed in the adult mouse brain. In the future, where and how sialylated O-linked glycoproteins function in the brain tissue remains to be clarified. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

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