O-GlcNAc Modification of the Extracellular Domain of Notch Receptors

Abstract

Epidermal growth factor (EGF) domains are posttranslationally modified with unique O-linked glycans. The classical types of O-glycans on EGF domains are O-fucose and O-glucose glycans, found on many plasma glycoproteins and signaling molecules, whose biological functions have been demonstrated especially in the context of the Notch signaling pathway. We recently discovered O-GlcNAc modification as a new modification of the EGF domain that occurs on the conserved Ser/Thr residue located between the fifth and sixth cysteine residues within the EGF domains of Notch receptors in Drosophila. Isolation of the unidentified enzyme responsible for the extracellular O-GlcNAcylation and characterization of the O-GlcNAc transferase gene will reveal the new biological roles for O-GlcNAcylation in secreted and membrane glycoproteins and the extracellular environment.