Univ. Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.
Cells. 2023 May 15;12(10):1396. doi: 10.3390/cells12101396.
The transport of proteins between the different cellular compartments and the cell surface is governed by the secretory pathway. Alternatively, unconventional secretion pathways have been described in mammalian cells, especially through multivesicular bodies and exosomes. These highly sophisticated biological processes rely on a wide variety of signaling and regulatory proteins that act sequentially and in a well-orchestrated manner to ensure the proper delivery of cargoes to their final destination. By modifying numerous proteins involved in the regulation of vesicular trafficking, post-translational modifications (PTMs) participate in the tight regulation of cargo transport in response to extracellular stimuli such as nutrient availability and stress. Among the PTMs, -GlcNAcylation is the reversible addition of a single N-acetylglucosamine monosaccharide (GlcNAc) on serine or threonine residues of cytosolic, nuclear, and mitochondrial proteins. -GlcNAc cycling is mediated by a single couple of enzymes: the -GlcNAc transferase (OGT) which catalyzes the addition of -GlcNAc onto proteins, and the -GlcNAcase (OGA) which hydrolyses it. Here, we review the current knowledge on the emerging role of -GlcNAc modification in the regulation of protein trafficking in mammalian cells, in classical and unconventional secretory pathways.
蛋白质在不同细胞区室和细胞表面之间的运输由分泌途径控制。此外，在哺乳动物细胞中已经描述了非常规的分泌途径，特别是通过多泡体和外泌体。这些高度复杂的生物过程依赖于广泛的信号和调节蛋白，它们依次以协调的方式发挥作用，以确保货物被正确地运送到它们的最终目的地。通过修饰参与囊泡运输调节的许多蛋白质，翻译后修饰 (PTMs) 参与了货物运输的紧密调节，以响应细胞外刺激，如营养物质的可用性和应激。在 PTMs 中，-GlcNAc 修饰是在细胞质、核和线粒体蛋白的丝氨酸或苏氨酸残基上可逆添加单个 N-乙酰葡萄糖胺单糖 (GlcNAc)。-GlcNAc 循环由一对酶介导：-GlcNAc 转移酶 (OGT) 催化将 -GlcNAc 添加到蛋白质上，-GlcNAcase (OGA) 水解它。在这里，我们综述了 -GlcNAc 修饰在调节哺乳动物细胞中经典和非常规分泌途径中蛋白质运输的新兴作用的最新知识。
