Dynamic O-GlcNAcylation of Sec23-interacting protein regulates COPII function
Tetsuya Hirata1, Quyen Nguyen1, Coco Liu1
1Department of Biochemistry, Duke University School of Medicine.
Biorxiv : the Preprint Server for Biology
|December 25, 2025
Summary
O-linked N-acetylglucosamine (O-GlcNAc) glycosylation of Sec23-interacting protein (Sec23IP) is crucial for regulating protein transport via COPII vesicles. This modification fine-tunes Sec23IP
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The secretory pathway is vital for eukaryotic protein trafficking.
- Coat protein complex II (COPII) mediates ER-to-Golgi transport via vesicles.
- Sec23-interacting protein (Sec23IP) links COPII inner and outer coats.
Purpose of the Study:
- To investigate the role of O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation in regulating Sec23IP function.
- To understand how O-GlcNAc modification impacts COPII vesicle formation and protein transport.
Main Methods:
- Validation of Sec23IP as an O-GlcNAcylated protein.
- Rescue experiments using a mutant Sec23IP deficient in glycosylation.
- Analysis of Sec23IP interaction with Sec31A during protein transport.
Main Results:
- O-GlcNAcylation of Sec23IP is essential for protein transport and Sec31A recruitment to ER exit sites (ERES).
- O-GlcNAcylation levels of Sec23IP increase during transport.
- Increased O-GlcNAcylation reduces Sec23IP's interaction with Sec31A.
Conclusions:
- Site-specific O-GlcNAcylation of Sec23IP spatiotemporally regulates its interaction with Sec31A.
- This modulation fine-tunes ER exit site recruitment and COPII assembly/disassembly.
- O-GlcNAc modification may govern COPII vesicle dynamics.
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