Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.224
Revised: January 20, 2014
Accepted: April 9, 2014
Published online: May 26, 2014
Processing time: 210 Days and 14.8 Hours
Core tip: The O-linked β-N-acetylglucosamine (O-GlcNAc) on extracellular protein domains is the most recently identified O-glycosylation of epidermal growth factor repeat-containing proteins such as Notch receptors. This O-GlcNAc modification occurs in the secretory pathway by an endoplasmic reticulum-resident O-GlcNAc transferase, extracellular O-linked β-N-acetylglucosamine (EOGT). In Drosophila, Dumpy, a membrane-tethered cuticle protein, was identified as a major O-GlcNAcylated protein that mediates the interaction between epithelial cells and the extracellular matrix. In mammals, extracellular O-GlcNAc was detected on Hspg2, Nell1, Lama5, Pamr1, and Notch receptors, although the physiological function of O-GlcNAc in mammals has not yet been elucidated. However, the recent finding that EOGT is a causative gene for Adams-Oliver syndrome provided important insights into the significance of extracellular O-GlcNAc in mammals. This review summarizes the current knowledge of extracellular O-GlcNAc and its implications in the pathological processes in Adams-Oliver syndrome.