PT  - JOURNAL ARTICLE
AU  - Brittany J. Bisnett
AU  - Brett M. Condon
AU  - Noah A. Linhart
AU  - Caitlin H. Lamb
AU  - Duc T. Huynh
AU  - Jingyi Bai
AU  - Timothy J. Smith
AU  - Jimin Hu
AU  - George R. Georgiou
AU  - Michael Boyce
TI  - Evidence for nutrient-dependent regulation of the COPII coat by O-GlcNAcylation
AID  - 10.1101/2020.12.30.424839
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.30.424839
4099  - http://biorxiv.org/content/early/2020/12/30/2020.12.30.424839.short
4100  - http://biorxiv.org/content/early/2020/12/30/2020.12.30.424839.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.5SGAc45SGlcNAcCIDcollision-induced dissociationCOPIIcoat protein II complexCRISPRclustered regularly interspaced short palindromic repeatsERendoplasmic reticulumETDelectron transfer dissociationHBPhexosamine biosynthetic pathwayIBimmunoblotIPimmunoprecipitationmTORCmechanistic target of rapamycin complexMSmass spectrometryO-GlcNAcO-linked β-N-acetylglucosamineOGAO-GlcNAcaseOGTO-GlcNAc transferasePTMspost-translational modificationsRaprapamycinTGThiamet-GUDP-GlcNAcuridine diphosphate-GlcNAc