Multiple roles for O-glycans in Notch signalling

Shweta Varshney, Pamela Stanley

Research output: Contribution to journalReview article

19 Scopus citations

Abstract

Notch signalling regulates a plethora of developmental processes and is also essential for the maintenance of tissue homeostasis in adults. Therefore, fine-tuning of Notch signalling strength needs to be tightly regulated. Of key importance for the regulation of Notch signalling are O-fucose, O-GlcNAc and O-glucose glycans attached to the extracellular domain of Notch receptors. The EGF repeats of the Notch receptor extracellular domain harbour consensus sites for addition of the different types of O-glycan to Ser or Thr, which takes place in the endoplasmic reticulum. Studies from Drosophila to mammals have demonstrated the multifaceted roles of O-glycosylation in regulating Notch signalling. O-glycosylation modulates different aspects of Notch signalling including recognition by Notch ligands, the strength of ligand binding, Notch receptor trafficking, stability and activation at the cell surface. Defects in O-glycosylation of Notch receptors give rise to pathologies in humans. This Review summarizes the nature of the O-glycans on Notch receptors and their differential effects on Notch signalling.

Original languageEnglish (US)
Pages (from-to)3819-3834
Number of pages16
JournalFEBS Letters
Volume592
Issue number23
DOIs
StatePublished - Dec 2018

Keywords

  • Notch signalling
  • O-GlcNAc
  • O-fucose
  • O-glucose
  • glycosylation
  • glycosyltransferases

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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