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Updated: Dec 23, 2025
11:36
Glycan Node Analysis: A Bottom-up Approach to Glycomics
Published on: May 22, 2016
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O-glycan initiation directs distinct biological pathways and controls epithelial differentiation
Ieva Bagdonaite1, Emil Mh Pallesen1, Zilu Ye1
1Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
EMBO Reports
|April 25, 2020
Summary
Loss of specific O-GalNAc transferases (GalNAc-Ts) in keratinocytes causes distinct epithelial phenotypes. Each GalNAc-T isoform impacts unique cellular pathways crucial for human epithelial tissue formation.
Area of Science:
- Biochemistry
- Cell Biology
- Glycobiology
Background:
- Post-translational modifications (PTMs) like O-glycosylation diversify protein function and regulation.
- O-GalNAc glycosylation, initiated by 20 GalNAc-transferases (GalNAc-Ts), is abundant and diverse.
- Deficiencies in GalNAc-Ts are linked to human diseases with distinct phenotypes in model organisms.
Purpose of the Study:
- To investigate the phenotypic consequences of losing individual dominant GalNAc-T isoforms in human keratinocytes.
- To explore cellular responses to GalNAc-T loss using transcriptomic, glycoproteomic, and phosphoproteomic analyses.
- To elucidate the specific roles of GalNAc-T isoforms in human epithelial tissue formation.
Main Methods:
- Generation of isogenic keratinocyte cell lines lacking specific GalNAc-T isoforms.
- Analysis of epithelial phenotypes formed by these keratinocytes.
- Global transcriptomic, differential glycoproteomic, and differential phosphoproteomic profiling.
Main Results:
- Loss of individual GalNAc-T isoforms resulted in distinct epithelial phenotypes.
- GalNAc-T1 loss affected endomembrane system components.
- GalNAc-T2 loss impacted cell-extracellular matrix adhesion.
- GalNAc-T3 loss influenced epithelial differentiation pathways.
Conclusions:
- GalNAc-T isoforms play specific, non-redundant roles in human epithelial tissue formation.
- Each GalNAc-T isoform targets distinct biological pathways.
- Understanding GalNAc-T functions is crucial for comprehending epithelial development and disease.
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