Evidence for Nutrient-dependent Regulation of the COPII Coat by O-GlcNAcylation

Overview

Journal Glycobiology

Date 2021 Jun 18

PMID 34142147

Citations 7

Authors

Brittany J Bisnett

Brett M Condon

Noah A Linhart

Caitlin H Lamb

Duc T Huynh

Jingyi Bai

Timothy J Smith

Jimin Hu

George R Georgiou

Michael Boyce

Affiliations

Soon will be listed here.

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.

Citing Articles

Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation.

Hu J, Huynh D, Dunn D, Wu J, Manriquez-Rodriguez C, Zhang Q bioRxiv. 2025; .

PMID: 40060460 PMC: 11888436. DOI: 10.1101/2025.02.27.640596.

O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder.

Matheny-Rabun C, Mokashi S, Radenkovic S, Wiggins K, Dukes-Rimsky L, Angel P Cell Rep. 2024; 43(11):114976.

PMID: 39561044 PMC: 11656453. DOI: 10.1016/j.celrep.2024.114976.

ER export via SURF4 uses diverse mechanisms of both client and coat engagement.

Maldutyte J, Li X, Gomez-Navarro N, Robertson E, Miller E J Cell Biol. 2024; 224(1).

PMID: 39531033 PMC: 11557686. DOI: 10.1083/jcb.202406103.

Neuronal activity-driven O-GlcNAcylation promotes mitochondrial plasticity.

Yu S, Wang H, Sanchez R, Carlson N, Nguyen K, Zhang A Dev Cell. 2024; 59(16):2143-2157.e9.

PMID: 38843836 PMC: 11338717. DOI: 10.1016/j.devcel.2024.05.008.

Nutrient deprivation alters the rate of COPII subunit recruitment at ER subdomains to tune secretory protein transport.

Kasberg W, Luong P, Swift K, Audhya A Nat Commun. 2023; 14(1):8140.

PMID: 38066006 PMC: 10709328. DOI: 10.1038/s41467-023-44002-7.

References

Aridor M . COPII gets in shape: Lessons derived from morphological aspects of early secretion. Traffic. 2018; 19(11):823-839. DOI: 10.1111/tra.12603. View

Bhandari D, Zhang J, Menon S, Lord C, Chen S, Helm J . Sit4p/PP6 regulates ER-to-Golgi traffic by controlling the dephosphorylation of COPII coat subunits. Mol Biol Cell. 2013; 24(17):2727-38. PMC: 3756924. DOI: 10.1091/mbc.E13-02-0114. View

Wansleeben C, Feitsma H, Montcouquiol M, Kroon C, Cuppen E, Meijlink F . Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b. Development. 2010; 137(7):1067-73. DOI: 10.1242/dev.041434. View

Teo C, Ingale S, Wolfert M, Elsayed G, Not L, Chatham J . Glycopeptide-specific monoclonal antibodies suggest new roles for O-GlcNAc. Nat Chem Biol. 2010; 6(5):338-43. PMC: 2857662. DOI: 10.1038/nchembio.338. View

Jin L, Pahuja K, Wickliffe K, Gorur A, Baumgartel C, Schekman R . Ubiquitin-dependent regulation of COPII coat size and function. Nature. 2012; 482(7386):495-500. PMC: 3292188. DOI: 10.1038/nature10822. View

Yuzwa S, Vocadlo D . O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer's disease and beyond. Chem Soc Rev. 2014; 43(19):6839-58. DOI: 10.1039/c4cs00038b. View

Pravata V, Omelkova M, Stavridis M, Desbiens C, Stephen H, Lefeber D . An intellectual disability syndrome with single-nucleotide variants in O-GlcNAc transferase. Eur J Hum Genet. 2020; 28(6):706-714. PMC: 7253464. DOI: 10.1038/s41431-020-0589-9. View

Lord C, Bhandari D, Menon S, Ghassemian M, Nycz D, Hay J . Sequential interactions with Sec23 control the direction of vesicle traffic. Nature. 2011; 473(7346):181-6. PMC: 3093450. DOI: 10.1038/nature09969. View

Hanover J, Wang P . O-GlcNAc cycling shows neuroprotective potential in C. elegans models of neurodegenerative disease. Worm. 2014; 2(4):e27043. PMC: 3917942. DOI: 10.4161/worm.27043. View

10.

Zacharogianni M, Aguilera-Gomez A, Veenendaal T, Smout J, Rabouille C . A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation. Elife. 2014; 3. PMC: 4270098. DOI: 10.7554/eLife.04132. View

11.

Darley-Usmar V, Ball L, Chatham J . Protein O-linked β-N-acetylglucosamine: a novel effector of cardiomyocyte metabolism and function. J Mol Cell Cardiol. 2011; 52(3):538-49. PMC: 3928598. DOI: 10.1016/j.yjmcc.2011.08.009. View

12.

Yuzwa S, Macauley M, Heinonen J, Shan X, Dennis R, He Y . A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol. 2008; 4(8):483-90. DOI: 10.1038/nchembio.96. View

13.

Wang S, Huang X, Sun D, Xin X, Pan Q, Peng S . Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt signaling. PLoS One. 2012; 7(5):e37427. PMC: 3358304. DOI: 10.1371/journal.pone.0037427. View

14.

Zou L, Zhu-Mauldin X, Marchase R, Paterson A, Liu J, Yang Q . Glucose deprivation-induced increase in protein O-GlcNAcylation in cardiomyocytes is calcium-dependent. J Biol Chem. 2012; 287(41):34419-31. PMC: 3464547. DOI: 10.1074/jbc.M112.393207. View

15.

Toleman C, Schumacher M, Yu S, Zeng W, Cox N, Smith T . Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins. Proc Natl Acad Sci U S A. 2018; 115(23):5956-5961. PMC: 6003352. DOI: 10.1073/pnas.1722437115. View

16.

Matsuoka K, Schekman R, Orci L, Heuser J . Surface structure of the COPII-coated vesicle. Proc Natl Acad Sci U S A. 2001; 98(24):13705-9. PMC: 61105. DOI: 10.1073/pnas.241522198. View

17.

Kettenbach A, Schweppe D, Faherty B, Pechenick D, Pletnev A, Gerber S . Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells. Sci Signal. 2011; 4(179):rs5. PMC: 3808085. DOI: 10.1126/scisignal.2001497. View

18.

Zachara N, Molina H, Wong K, Pandey A, Hart G . The dynamic stress-induced "O-GlcNAc-ome" highlights functions for O-GlcNAc in regulating DNA damage/repair and other cellular pathways. Amino Acids. 2010; 40(3):793-808. PMC: 3329784. DOI: 10.1007/s00726-010-0695-z. View

19.

Stagg S, Gurkan C, Fowler D, LaPointe P, Foss T, Potter C . Structure of the Sec13/31 COPII coat cage. Nature. 2006; 439(7073):234-8. DOI: 10.1038/nature04339. View

20.

Salama N, Chuang J, Schekman R . Sec31 encodes an essential component of the COPII coat required for transport vesicle budding from the endoplasmic reticulum. Mol Biol Cell. 1997; 8(2):205-17. PMC: 276074. DOI: 10.1091/mbc.8.2.205. View