Department of Biochemistry and Biophysics, AgriLife Research, Texas A&M University, College Station, College Station, TX 77843, United States.
Glycobiology. 2023 Dec 25;33(11):911-926. doi: 10.1093/glycob/cwad067.
Recent research has unveiled numerous important functions of protein glycosylation in development, homeostasis, and diseases. A type of glycosylation taking the center stage is protein O-mannosylation, a posttranslational modification conserved in a wide range of organisms, from yeast to humans. In animals, protein O-mannosylation plays a crucial role in the nervous system, whereas protein O-mannosylation defects cause severe neurological abnormalities and congenital muscular dystrophies. However, the molecular and cellular mechanisms underlying protein O-mannosylation functions and biosynthesis remain not well understood. This review outlines recent studies on protein O-mannosylation while focusing on the functions in the nervous system, summarizes the current knowledge about protein O-mannosylation biosynthesis, and discusses the pathologies associated with protein O-mannosylation defects. The evolutionary perspective revealed by studies in the Drosophila model system are also highlighted. Finally, the review touches upon important knowledge gaps in the field and discusses critical questions for future research on the molecular and cellular mechanisms associated with protein O-mannosylation functions.
最近的研究揭示了蛋白质糖基化在发育、内稳态和疾病中的许多重要功能。一种处于中心地位的糖基化类型是蛋白质 O-甘露糖基化，这是一种在从酵母到人类等广泛生物中保守的翻译后修饰。在动物中，蛋白质 O-甘露糖基化在神经系统中起着至关重要的作用，而蛋白质 O-甘露糖基化缺陷会导致严重的神经异常和先天性肌肉营养不良。然而，蛋白质 O-甘露糖基化功能和生物合成的分子和细胞机制仍未得到很好的理解。本综述概述了蛋白质 O-甘露糖基化的最新研究，重点介绍了其在神经系统中的功能，总结了目前关于蛋白质 O-甘露糖基化生物合成的知识，并讨论了与蛋白质 O-甘露糖基化缺陷相关的病理学。还强调了果蝇模型系统研究揭示的进化视角。最后，该综述还涉及该领域的重要知识空白，并讨论了与蛋白质 O-甘露糖基化功能相关的分子和细胞机制的未来研究的关键问题。
