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Increased bisecting and core-fucosylated N-glycans on mutant human amyloid precursor proteins

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Abstract

Alteration of glycoprotein glycans often changes various properties of the glycoprotein. To understand the significance of N-glycosylation in the pathogenesis of early-onset familial Alzheimer’s disease (AD) and in β-amyloid (Aβ) production, we examined whether the mutations in the amyloid precursor protein (APP) gene found in familial AD affect the N-glycans on APP. We purified the secreted forms of wild-type and mutant human APPs (both the Swedish type and the London type) produced by transfected C17 cells and determined the N-glycan structures of these three recombinant APPs. Although the major N-glycan species of the three APPs were similar, both mutant APPs contained higher contents of bisecting N-acetylglucosamine and core-fucose residues as compared to wild-type APP. These results demonstrate that familial AD mutations in the polypeptide backbone of APP can affect processing of the attached N-glycans; however, whether these changes in N-glycosylation affect Aβ production remains to be established.

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Abbreviations

AB:

aminobezamide

Aβ:

β-amyloid

AD:

Alzheimer’s disease

APP:

amyloid precursor protein

FUT8:

α1–6 fucosyltransferase

GnT-III:

N-acetylglucosaminyltransferase III

HPLC:

high-performance liquid chromatography

GU:

glucose unit

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Acknowledgement

We would like to thank Dr. Takashi Muramatsu for providing an endo-β-galactosidase C. This study was supported by a Grant-in-Aid for Scientific Research (20390031) from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Glycobiology Research Group, Tokyo Metropolitan Institute of Gerontology, Foundation for Research on Aging and Promotion of Human Welfare, 35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan

    Keiko Akasaka-Manya, Hiroshi Manya, Yoko Sakurai & Tamao Endo

  2. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA

    Boguslaw S. Wojczyk & Steven L. Spitalnik

Authors
  1. Keiko Akasaka-Manya
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  2. Hiroshi Manya
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  3. Yoko Sakurai
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  4. Boguslaw S. Wojczyk
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  5. Steven L. Spitalnik
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  6. Tamao Endo
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Corresponding author

Correspondence to Tamao Endo.

Additional information

Keiko Akasaka-Manya and Hiroshi Manya contributed equally to this work.

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Akasaka-Manya, K., Manya, H., Sakurai, Y. et al. Increased bisecting and core-fucosylated N-glycans on mutant human amyloid precursor proteins. Glycoconj J 25, 775–786 (2008). https://doi.org/10.1007/s10719-008-9140-x

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  • DOI: https://doi.org/10.1007/s10719-008-9140-x

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