Evidence for nutrient-dependent regulation of the COPII coat by O-GlcNAcylation

• Published in: Glycobiology (Oxford) 2021-09, Vol.31 (9), p.1102-1120
• Main Authors: Bisnett, Brittany J, Condon, Brett M, Linhart, Noah A, Lamb, Caitlin H, Huynh, Duc T, Bai, Jingyi, Smith, Timothy J, Hu, Jimin, Georgiou, George R, Boyce, Michael
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - metabolism; Animals; Cell Biology; Editor's Choice; Endoplasmic Reticulum - metabolism; Glycosylation; Mammals - metabolism; N-Acetylglucosaminyltransferases - metabolism; Nutrients; Protein Processing, Post-Translational; Signal Transduction
• ISSN: 1460-2423; 0959-6658; 1460-2423
• DOI: 10.1093/glycob/cwab055

Abstract O-linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic form of intracellular glycosylation common in animals, plants and other organisms. O-GlcNAcylation is essential in mammalian cells and is dysregulated in myriad human diseases, such as cancer, neurodegeneration and metabolic syndrome. Despite this pathophysiological significance, key aspects of O-GlcNAc signaling remain incompletely understood, including its impact on fundamental cell biological processes. Here, we investigate the role of O-GlcNAcylation in the coat protein II complex (COPII), a system universally conserved in eukaryotes that mediates anterograde vesicle trafficking from the endoplasmic reticulum. We identify new O-GlcNAcylation sites on Sec24C, Sec24D and Sec31A, core components of the COPII system, and provide evidence for potential nutrient-sensitive pathway regulation through site-specific glycosylation. Our work suggests a new connection between metabolism and trafficking through the conduit of COPII protein O-GlcNAcylation.