Loibl Martin, Strahl Sabine
University of Heidelberg, Heidelberg, Germany.
Biochim Biophys Acta. 2013 Nov;1833(11):2438-46. doi: 10.1016/j.bbamcr.2013.02.008. Epub 2013 Feb 20.
Protein O-mannosylation is a vital type of glycosylation that is conserved among fungi, animals, and humans. It is initiated in the endoplasmic reticulum (ER) where the synthesis of the mannosyl donor substrate and the mannosyltransfer to proteins take place. O-mannosylation defects interfere with cell wall integrity and ER homeostasis in yeast, and define a pathomechanism of severe neuromuscular diseases in humans.
On the molecular level, the O-mannosylation pathway and the function of O-mannosyl glycans have been characterized best in the eukaryotic model yeast Saccharomyces cerevisiae. In this review we summarize general features of protein O-mannosylation, including biosynthesis of the mannosyl donor, characteristics of acceptor substrates, and the protein O-mannosyltransferase machinery in the yeast ER. Further, we discuss the role of O-mannosyl glycans and address the question why protein O-mannosylation is essential for viability of yeast cells.
Understanding of the molecular mechanisms of protein O-mannosylation in yeast could lead to the development of novel antifungal drugs. In addition, transfer of the knowledge from yeast to mammals could help to develop diagnostic and therapeutic approaches in the frame of neuromuscular diseases. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.
蛋白质O-甘露糖基化是一种重要的糖基化类型，在真菌、动物和人类中保守存在。它在内质网（ER）中起始，甘露糖基供体底物的合成以及甘露糖基向蛋白质的转移在此发生。O-甘露糖基化缺陷会干扰酵母中的细胞壁完整性和内质网稳态，并确定人类严重神经肌肉疾病的发病机制。
在分子水平上，O-甘露糖基化途径和O-甘露糖基聚糖的功能在真核模式酵母酿酒酵母中得到了最好的表征。在本综述中，我们总结了蛋白质O-甘露糖基化的一般特征，包括甘露糖基供体的生物合成、受体底物的特征以及酵母内质网中的蛋白质O-甘露糖基转移酶机制。此外，我们讨论了O-甘露糖基聚糖的作用，并探讨了为什么蛋白质O-甘露糖基化对酵母细胞的生存能力至关重要的问题。
了解酵母中蛋白质O-甘露糖基化的分子机制可能会导致新型抗真菌药物的开发。此外，将知识从酵母转移到哺乳动物有助于在神经肌肉疾病框架内开发诊断和治疗方法。本文是名为：内质网的功能和结构多样性的特刊的一部分。
