Jaiswal Ruchi, Liu Yimin, Petriello Michael, Zhang Xiangmin, Yi Zhengping, Fehl Charlie
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy, Wayne State University, 259 Mack Avenue, Detroit, Michigan 48201, United States.
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States.
Glycobiology. 2025 Jan 24;35(3). doi: 10.1093/glycob/cwaf005.
A key nutrient sensing process in all animal tissues is the dynamic attachment of O-linked N-acetylglucosamine (O-GlcNAc). Determining the targets and roles of O-GlcNAc glycoproteins has the potential to reveal insights into healthy and diseased metabolic states. In cell studies, thousands of proteins are known to be O-GlcNAcylated, but reference datasets for most tissue types in animals are lacking. Here, we apply a chemoenzymatic labeling study to compile a high coverage dataset of quadriceps skeletal muscle O-GlcNAc glycoproteins from mice. Our dataset contains over 550 proteins, and > 80% of the dataset matched known O-GlcNAc proteins. This dataset was further annotated via bioinformatics, revealing the distribution, protein interactions, and gene ontology (GO) functions of these skeletal muscle proteins. We compared these quadriceps glycoproteins with a high-coverage O-GlcNAc enrichment profile from mouse hearts and describe the key overlap and differences between these tissue types. Quadriceps muscles can be used for biopsies, so we envision this dataset to have potential biomedical relevance in detecting aberrant glycoproteins in metabolic diseases and physiological studies. This new knowledge adds to the growing collection of tissues with high-coverage O-GlcNAc profiles, which we anticipate will further the systems biology of O-GlcNAc mechanisms, functions, and roles in disease.
所有动物组织中一个关键的营养感知过程是O-连接的N-乙酰葡糖胺(O-GlcNAc)的动态附着。确定O-GlcNAc糖蛋白的靶点和作用有可能揭示对健康和患病代谢状态的见解。在细胞研究中,已知数千种蛋白质会发生O-GlcNAc糖基化,但缺乏动物大多数组织类型的参考数据集。在这里,我们应用化学酶标记研究来编制来自小鼠股四头肌骨骼肌O-GlcNAc糖蛋白的高覆盖率数据集。我们的数据集中包含超过550种蛋白质,并且超过80%的数据与已知的O-GlcNAc蛋白匹配。该数据集通过生物信息学进一步注释,揭示了这些骨骼肌蛋白的分布、蛋白质相互作用和基因本体(GO)功能。我们将这些股四头肌糖蛋白与来自小鼠心脏的高覆盖率O-GlcNAc富集图谱进行比较,并描述了这些组织类型之间的关键重叠和差异。股四头肌可用于活检,因此我们设想该数据集在检测代谢疾病和生理学研究中的异常糖蛋白方面具有潜在的生物医学相关性。这一新知识增加了具有高覆盖率O-GlcNAc图谱组织的不断增长的集合中,我们预计这将进一步推动O-GlcNAc机制、功能及其在疾病中的作用的系统生物学研究。