Extracellular O-GlcNAc: From Discovery to Current Developments

Abstract

My group has discovered extracellular O-GlcNAc on the epidermal growth factor repeats of Notch receptors. Unlike OGT-dependent O-GlcNAcylation, extracellular O-GlcNAc occurs in the endoplasmic reticulum by the action of EOGT. Genetic inactivation of eogt in Drosophila revealed that extracellular O-GlcNAc is essential for developmental processes and appears to regulate the function of apical extracellular molecules such as Dumpy. In contrast, extracellular O-GlcNAc is required for the precise control of Notch signaling in mammals. Eogt mutant mice show defects in retinal vascular integrity. Importantly, mutations in EOGT cause Adams-Oliver syndrome, a congenital disorder in humans. These findings indicate diverse but essential biological functions of extracellular O-GlcNAc in Drosophila and mammals. In this article, I will give an overview of the biochemical and biological studies of extracellular O-GlcNAc, summarizing previous findings and current developments.