Panin Vladislav M, Wells Lance
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas.
Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia.
Curr Protoc Protein Sci. 2014 Feb 3;75:12.12.1-12.12.29. doi: 10.1002/0471140864.ps1212s75.
Protein O-mannosylation is a special type of glycosylation that plays prominent roles in metazoans, affecting development and physiology of the nervous system and muscles. A major biological effect of O-mannosylation involves the regulation of α-dystroglycan, a membrane glycoprotein mediating cell-extracellular matrix interactions. Genetic defects of O-mannosylation result in the loss of ligand-binding activity of α-dystroglycan and cause congenital muscular dystrophies termed dystroglycanopathies. Recent progress in mass spectrometry and in vitro analyses has shed new light on the mechanism of α-dystroglycan glycosylation; however, this mechanism is underlain by complex genetic and molecular elements that remain poorly understood. Protein O-mannosylation is evolutionarily conserved in metazoans, yet the pathway is simplified and more amenable to genetic analyses in invertebrate organisms, indicating that genetically tractable in vivo models could facilitate research in this area. This unit describes recent methodological strategies for studying protein O-mannosylation using in vitro and in vivo approaches.
蛋白质O-甘露糖基化是一种特殊的糖基化类型，在后生动物中发挥着重要作用，影响神经系统和肌肉的发育及生理功能。O-甘露糖基化的一个主要生物学效应涉及对α- dystroglycan的调节，α- dystroglycan是一种介导细胞与细胞外基质相互作用的膜糖蛋白。O-甘露糖基化的遗传缺陷会导致α- dystroglycan配体结合活性丧失，并引发称为糖基化肌营养不良症的先天性肌营养不良。质谱分析和体外分析的最新进展为α- dystroglycan糖基化机制提供了新的线索；然而，这一机制是由复杂的遗传和分子因素构成的，目前仍知之甚少。蛋白质O-甘露糖基化在后生动物中具有进化保守性，但该途径在无脊椎动物中更为简化，更适合进行遗传分析，这表明易于进行遗传操作的体内模型有助于该领域的研究。本单元介绍了使用体外和体内方法研究蛋白质O-甘露糖基化的最新方法策略。
