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Precision mapping of the human O‐GalNAc glycoproteome through SimpleCell technology

Steentoft, Catharina, Vakhrushev, Sergey Y, Joshi, Hiren J, Kong, Yun, Vester‐Christensen, Malene B, Schjoldager, Katrine T‐B G, Lavrsen, Kirstine, Dabelsteen, Sally, Pedersen, Nis B, Marcos‐Silva, Lara, Gupta, Ramneek, Paul Bennett, Eric, Mandel, Ulla, Brunak, Søren, Wandall, Hans H, Levery, Steven B, Clausen, Henrik·2013·The EMBO Journal
DOI 10.1038/emboj.2013.79
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Abstract

Glycosylation is the most abundant and diverse posttranslational modification of proteins. While several types of glycosylation can be predicted by the protein sequence context, and substantial knowledge of these glycoproteomes is available, our knowledge of the GalNAc-type O-glycosylation is highly limited. This type of glycosylation is unique in being regulated by 20 polypeptide GalNAc-transferases attaching the initiating GalNAc monosaccharides to Ser and Thr (and likely some Tyr) residues. We have developed a genetic engineering approach using human cell lines to simplify O-glycosylation (SimpleCells) that enables proteome-wide discovery of O-glycan sites using 'bottom-up' ETD-based mass spectrometric analysis. We implemented this on 12 human cell lines from different organs, and present a first map of the human O-glycoproteome with almost 3000 glycosites in over 600 O-glycoproteins as well as an improved NetOGlyc4.0 model for prediction of O-glycosylation. The finding of unique subsets of O-glycoproteins in each cell line provides evidence that the O-glycoproteome is differentially regulated and dynamic. The greatly expanded view of the O-glycoproteome should facilitate the exploration of how site-specific O-glycosylation regulates protein function.

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Crossref · 10.1038/emboj.2013.79

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  • Newly synthesized SorLA molecules follow the constitutive secretory pathway from the ER to the cell surface through the Golgi, and undergo post-translational modifications and maturation, resulting in immature and mature species.

    “Newly synthesized SorLA molecules follow the constitutive secretory pathway from the endoplasmic reticulum (ER) to the cell surface, through the Golgi. During their transport through the secretory pathway, SorLA proteins are subjected to several post-translational modifications, including both N- and O-glycosylation, and maturation processes [3–9], resulting in the presence of immature and mature”

    From Impaired SorLA maturation and trafficking as a new mechanism for SORL1 missense variants in Alzheimer disease (2021) · cites this paper as [7]

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Metadata

Authors
Steentoft, C., Vakhrushev, S. Y., Joshi, H. J., Kong, Y., Vester‐Christensen, M. B., Schjoldager, K. T. G., Lavrsen, K., Dabelsteen, S., Pedersen, N. B., Marcos‐Silva, L., Gupta, R., Paul Bennett, E., Mandel, U., Brunak, S., Wandall, H. H., Levery, S. B., & Clausen, H.
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2013-04-12
Volume
32
Issue
10
Pages
1478-1488
ISSN
  • 0261-4189
  • 1460-2075
DOI
10.1038/emboj.2013.79
Cited by
1,408
References
5
Language
en
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