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Multiple roles for O-glycans in Notch signalling.
Shweta Varshney1, Pamela Stanley1
1Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, USA.
FEBS Letters
|September 13, 2018
Summary
O-glycosylation, involving O-fucose, O-GlcNAc, and O-glucose, is crucial for regulating Notch signalling strength. These modifications impact ligand binding, receptor stability, and activation, with defects leading to human pathologies.
Area of Science:
- Cellular biology
- Developmental biology
- Glycobiology
Background:
- Notch signalling is vital for development and adult tissue homeostasis.
- Tight regulation of Notch signalling strength is essential.
- O-glycans (O-fucose, O-GlcNAc, O-glucose) on Notch receptors are key regulators.
Purpose of the Study:
- To review the nature of O-glycans on Notch receptors.
- To summarize their differential effects on Notch signalling.
- To highlight the role of O-glycosylation in Notch pathway regulation.
Main Methods:
- Review of existing literature on Notch signalling and O-glycosylation.
- Analysis of studies from Drosophila to mammals.
- Focus on O-glycan addition sites and their functional impact.
Main Results:
- O-glycosylation occurs on Ser/Thr within EGF repeats in the endoplasmic reticulum.
- O-glycans modulate Notch ligand recognition, binding affinity, trafficking, stability, and activation.
- Dysregulation of Notch O-glycosylation is linked to human diseases.
Conclusions:
- O-glycosylation is a critical modulator of Notch receptor function.
- Understanding these glycan structures and their roles is essential for comprehending Notch signalling.
- Aberrant O-glycosylation contributes to human pathologies, underscoring its clinical relevance.
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