The posttranslational glycosylation of select proteins by O-linked mannose (O-mannose or O-man) is a conserved modification from yeast to humans and has been shown to be necessary for proper development and growth. The most well studied O-mannosylated mammalian protein is α-dystroglycan. Hypoglycosylation of α-dystroglycan results in varying severities of congenital muscular dystrophies, cancer progression and metastasis, and inhibited entry and infection of certain arenaviruses. Defects in the gene products responsible for post-translational modification of α-dystroglycan, primarily glycosyltransferases, are the basis for these diseases. The multitude of clinical phenotypes resulting from defective O-mannosylation highlights the biomedical significance of this unique modification. Elucidation of the various O-mannose biosynthetic pathways is imperative to understanding a broad range of human diseases and for the development of novel therapeutics. In this review, we will focus on recent discoveries delineating the various enzymes, structures, and functions associated with O-mannose-initiated glycoproteins. Additionally, we discuss current gaps in our knowledge of mammalian O-mannosylation, discuss the evolution of this pathway, and illustrate the utility and limitations of model systems to study functions of O-mannosylation.

中文翻译：

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在了解哺乳动物O-甘露糖基化方面的最新进展

通过O-连接的甘露糖（O-甘露糖或O- man）对所选蛋白质进​​行的翻译后糖基化是从酵母到人的保守修饰，并且已经证明对于适当的发育和生长是必需的。研究最深入的O-甘露糖基化哺乳动物蛋白是α-dystroglycan。α-dystroglycan的低糖基化会导致先天性肌营养不良的严重程度不同，癌症的进展和转移，并抑制某些沙粒病毒的进入和感染。这些疾病的基础是负责α-dystroglycan翻译后修饰的基因产物中的缺陷，主要是糖基转移酶。O缺陷导致的众多临床表型-甘露糖基化突出了这种独特修饰的生物医学意义。阐明各种O-甘露糖生物合成途径对于理解广泛的人类疾病和开发新的治疗方法是必不可少的。在这篇综述中，我们将集中于描述与O-甘露糖引发的糖蛋白相关的各种酶，结构和功能的最新发现。此外，我们讨论了哺乳动物O-甘露糖基化知识的当前差距，讨论了该途径的演变，并阐明了研究O-甘露糖基化功能的模型系统的实用性和局限性。