Related Experiment Video
Updated: Aug 6, 2026
09:07
Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
Published on: March 17, 2014
Dynamic O-GlcNAcylation of Sec23-interacting protein regulates COPII function
Tetsuya Hirata1, Quyen Nguyen1, Coco Liu1
1Department of Biochemistry, Duke University School of Medicine.
The Journal of Biological Chemistry
|July 22, 2026
Summary
O-linked N-acetylglucosamine (O-GlcNAc) modifies Sec23-interacting protein (Sec23IP), regulating protein transport via the COPII pathway. This glycosylation fine-tunes Sec23IP
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The secretory pathway is crucial for eukaryotic protein trafficking, with COPII (coat protein complex II) mediating transport from the ER.
- Sec23IP acts as a linker between COPII inner (Sec23-Sec24) and outer (Sec13-Sec31) layers, suggesting a regulatory role in COPII function.
- Mechanisms controlling Sec23IP activity, particularly its regulation by post-translational modifications, are not well understood.
Purpose of the Study:
- To investigate the role of O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation in regulating Sec23IP function.
- To determine how O-GlcNAc modification of Sec23IP impacts COPII-mediated protein transport and ER exit site (ERES) dynamics.
Main Methods:
- Validation of Sec23IP as an O-GlcNAcylated protein.
- Rescue experiments using a mutant Sec23IP protein with impaired glycosylation in knockout cells.
- Analysis of Sec23IP-Sec31A interactions and recruitment to ERES under varying conditions.
Main Results:
- Sec23IP is confirmed as a bona fide O-GlcNAcylated protein.
- O-GlcNAcylation of Sec23IP is essential for efficient protein transport and Sec31A recruitment to ERES.
- Increased O-GlcNAcylation of Sec23IP during transport correlates with decreased Sec31A interaction, suggesting dynamic regulation.
Conclusions:
- Site-specific O-GlcNAcylation of Sec23IP spatiotemporally modulates its interaction with Sec31A.
- This dynamic regulation fine-tunes ERES recruitment and COPII assembly/disassembly, impacting protein transport.
- O-GlcNAc modification may be a general mechanism for regulating COPII components and vesicle formation.
Related Concept Videos
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:33Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...