O-Glycans in Mammalian Notch Signaling

Abstract

Notch signaling occurs following the activation of membrane-bound Notch receptors by canonical Notch ligands expressed in neighboring cells. It is a fundamental requirement for the regulation of cell fate decisions during organellar differentiation in mammals. The extracellular domain of Notch receptors comprises numerous epidermal growth factor-like (EGF) repeats, many of which are modified by glycans O-linked to Ser or Thr at specific consensus sites. This chapter will summarize the nature and functions of O-Fucose, O-Glucose, O-GlcNAc, and O-GalNAc glycans in mammalian cells, mouse development, and human disease. Congenital diseases that arise from reduced addition of O-glycans reveal the importance of these modifications for Notch signaling.