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

Glycobiology. 2021 Sep 20;31(9):1102-1120. doi: 10.1093/glycob/cwab055.


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.

Keywords: COPII; Membrane trafficking; Nutrient signaling; O-GlcNAc.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylglucosamine* / metabolism
  • Animals
  • Endoplasmic Reticulum* / metabolism
  • Glycosylation
  • Mammals / metabolism
  • N-Acetylglucosaminyltransferases / metabolism
  • Nutrients
  • Protein Processing, Post-Translational
  • Signal Transduction


  • N-Acetylglucosaminyltransferases
  • Acetylglucosamine