Extracellular O-linked β-N-acetylglucosamine: Its biology and relationship to human disease

• 作者: Koichi Furukawa Mitsutaka Ogawa Tetsuya Okajima
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: EXTRACELLULAR O-linked β-N-acetylglucosamine NOTCH Adams-Oliver syndrome
• 年，卷（期）: 2014,（2）
• 页码范围: 224-230
• 页数: 7页
• 分类号: R682

摘要

The O-linked β-N-acetylglucosamine(O-GlcNAc)ylation of cytoplasmic and nuclear proteins regulates basic cellular functions and is involved in the etiology of neurodegeneration and diabetes. Intracellular O-GlcNAcylation is catalyzed by a single O-GlcNAc transferase, O-GlcNAc transferase(OGT). Recently, an atypical O-GlcNAc transferase, extracellular O-linked β-N-acetylglucosamine(EOGT), which is responsible for the modification of extracellular O-GlcNAc, was identified. Although both OGT and EOGT are regulated through the common hexosamine biosynthesis pathway, EOGT localizes to the lumen of the endoplasmic reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT-independent manner. In Drosophila, loss of Eogt gives phenotypes similar to those caused by defects in the apical extracellular matrix. Dumpy, a membrane-anchored apical extracellular matrix protein, was identified as a major O-GlcNAcylated protein, and EOGT mediates Dumpy-dependent cell adhesion. In mammals, extracellular O-GlcNAc was detected on extracellular proteins including heparan sulfate proteoglycan 2, Nell1, laminin subunit alpha-5, Pamr1, and transmembrane proteins, including Notch receptors. Although the physiological function of O-GlcNAc in mammals has not yet been elucidated, exome sequencing identified homozygous EOGT mutations in patients with Adams-Oliver syndrome, a rare congenital disorder characterized by aplasia cutis congenita and terminal transverse limb defects. This review summarizes the current knowledge of extracellular O-GlcNAc and its implications in the pathological processes in Adams-Oliver syndrome.