N-acetylglucosamine modification in the lumen of the endoplasmic reticulum.
N-acetylglucosamine modification in the lumen of the endoplasmic reticulum.
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DOI：
10.1016/j.bbagen.2015.03.003
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发表时间：
2015-06
期刊：
影响因子：
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通讯作者：
Mitsutaka Ogawa;Shogo Sawaguchi;K. Furukawa;T. Okajima
中科院分区：
文献类型：
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作者：
Mitsutaka Ogawa;Shogo Sawaguchi;K. Furukawa;T. Okajima
背景由表皮生长因子结构域O-β-N-乙酰氨基葡萄糖(O-GlcNAc)催化的表皮生长因子结构域的O-GlcNAc修饰是第一例内质网(ER)管腔内的O-GlcNAc修饰。本文综述了近年来通过生化特征、果蝇遗传分析和人类EOGT突变鉴定获得的对EGF域的O-GlcNAc修饰。此外，本综述还讨论了GTDC2--另一种与EOGT同源的ER蛋白，它催化O-甘露糖化α-营养不良聚糖的GlcNAc修饰--以及参与内质网腔内GlcNAc修饰的生物合成途径的其他成分。此外，内质网管腔中GlcNAc的异常修饰是导致Adams-Oliver综合征和Walker-Warburg综合征的原因。一般意义了解内质网管腔中GlcNAc修饰的生物学功能将为了解O-聚糖的独特作用提供新的见解，O-聚糖在多功能糖蛋白中的重要性已被证明，如Notch受体和α-dystrolyan。
BackgroundO-linked β-N-acetylglucosamine (O-GlcNAc) modification of epidermal growth factor (EGF) domains catalyzed by EGF domain O-GlcNAc transferase (EOGT) is the first example of GlcNAc modification in the lumen of the endoplasmic reticulum (ER).Scope of reviewThis review summarizes current knowledge on the EOGT-catalyzed O-GlcNAc modification of EGF domains obtained through biochemical characterization, genetic analysis inDrosophila, and identification of humanEOGTmutation. Additionally, this review discusses GTDC2—another ER protein homologous to EOGT that catalyzes the GlcNAc modification of O-mannosylated α-dystroglycan—and other components of the biosynthetic pathway involved in GlcNAc modification in the ER lumen.Major conclusionsGlcNAc modification in the ER lumen has been identified as a novel type of protein modification that regulates specific protein function. Moreover, abnormal GlcNAc modification in the ER lumen is responsible for Adams–Oliver syndrome and Walker–Warburg syndrome.General significanceElucidation of the biological function of GlcNAc modification in the ER lumen will provide new insights into the unique roles of O-glycans, whose importance has been demonstrated in multifunctional glycoproteins such as Notch receptors and α-dystroglyan.