Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction. Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy. Despite this pathophysiological significance, how cells regulate IF structure, dynamics, and function remains poorly understood. Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration. In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche. Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.

中文翻译：

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位点特异性糖基化调节中间丝细胞骨架的形式和功能

中间丝 (IF) 是后生动物细胞骨架的主要组成部分，对正常细胞形态、运动和信号转导至关重要。IF 的失调会导致多种人类疾病，包括皮肤病、心肌病、脂肪营养不良和神经病。尽管有这种病理生理学意义，但细胞如何调节 IF 结构、动力学和功能仍然知之甚少。在这里，我们展示了原型 IF 蛋白波形蛋白与 O-连接的 β-N-乙酰氨基葡萄糖 (O-GlcNAc) 的位点特异性修饰介导了其同型蛋白质 - 蛋白质相互作用，并且是人类细胞中 IF 形态和细胞迁移所必需的。此外，我们发现细胞内病原体沙眼衣原体在感染过程中重塑宿主 IF 细胞骨架，需要特定的波形蛋白糖基化位点和 O-GlcNAc 转移酶活性来维持其复制生态位。我们的结果为波形蛋白 O-GlcNAcylation 的生化和细胞生物学功能提供了新的见解，并且可能对我们对 IF 蛋白的总体调控的理解具有广泛的意义。