O-glycan initiation directs distinct biological pathways and controls epithelial differentiation
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- O‐glycan initiation directs distinct biological pathways and controls epithelial differentiation
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Post-translational modifications (PTMs) greatly expand the function and potential for regulation of protein activity, and O-glycosylation is among the most abundant and diverse PTMs. Initiation of O-GalNAc glycosylation is regulated by 20 distinct GalNAc-transferases (GalNAc-Ts), and deficiencies in individual GalNAc-Ts are associated with human disease, causing subtle but distinct phenotypes in model organisms. Here, we generate a set of isogenic keratinocyte cell lines lacking either of the three dominant and differentially expressed GalNAc-Ts. Through the ability of keratinocytes to form epithelia, we investigate the phenotypic consequences of the loss of individual GalNAc-Ts. Moreover, we probe the cellular responses through global transcriptomic, differential glycoproteomic, and differential phosphoproteomic analyses. We demonstrate that loss of individual GalNAc-T isoforms causes distinct epithelial phenotypes through their effect on specific biological pathways; GalNAc-T1 targets are associated with components of the endomembrane system, GalNAc-T2 targets with cell–ECM adhesion, and GalNAc-T3 targets with epithelial differentiation. Thus, GalNAc-T isoforms serve specific roles during human epithelial tissue formation.
Original language | English |
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Article number | e48885 |
Journal | EMBO Reports |
Volume | 21 |
Issue number | 6 |
Number of pages | 17 |
ISSN | 1469-221X |
DOIs | |
Publication status | Published - 2020 |
- 3D skin, differential glycoproteomics, polyomics, polypeptide GalNAc-transferase, tissue development
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