Mining the O-mannose glycoproteome reveals cadherins as major O-mannosylated glycoproteins
Research output: Contribution to journal › Journal article › Research › peer-review
The metazoan O-mannose (O-Man) glycoproteome is largely unknown. It has been shown that up to 30% of brain O-glycans are of the O-Man type, but essentially only alpha-dystroglycan (α-DG) of the dystrophin-glycoprotein complex is well characterized as an O-Man glycoprotein. Defects in O-Man glycosylation underlie congenital muscular dystrophies and considerable efforts have been devoted to explore this O-glycoproteome without much success. Here, we used our SimpleCell strategy using nuclease-mediated gene editing of a human cell line (MDA-MB-231) to reduce the structural heterogeneity of O-Man glycans and to probe the O-Man glycoproteome. In this breast cancer cell line we found that O-Man glycosylation is primarily found on cadherins and plexins on β-strands in extracellular cadherin and Ig-like, plexin and transcription factor domains. The positions and evolutionary conservation of O-Man glycans in cadherins suggest that they play important functional roles for this large group of cell adhesion glycoproteins, which can now be addressed. The developed O-Man SimpleCell strategy is applicable to most types of cell lines and enables proteome-wide discovery of O-Man protein glycosylation.
Original language | English |
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Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 110 |
Issue number | 52 |
Pages (from-to) | 21018-23 |
Number of pages | 6 |
ISSN | 0027-8424 |
DOIs | |
Publication status | Published - 24 Dec 2013 |
- Cadherins, Cell Adhesion Molecules, Cell Line, Tumor, Glycoproteins, Glycosylation, Humans, Mannose, Mass Spectrometry, Nerve Tissue Proteins, Proteome, Proteomics
Research areas
ID: 108666794