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Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway.

Publication ,  Journal Article
Cox, NJ; Unlu, G; Bisnett, BJ; Meister, TR; Condon, BM; Luo, PM; Smith, TJ; Hanna, M; Chhetri, A; Soderblom, EJ; Audhya, A; Knapik, EW; Boyce, M
Published in: Biochemistry
January 9, 2018

The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing and maintaining normal cell and tissue homeostasis. Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. However, little is known about how vertebrates dynamically regulate COPII activity in response to developmental, metabolic, or pathological cues. Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway.

Duke Scholars

Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

January 9, 2018

Volume

57

Issue

1

Start / End Page

91 / 107

Location

United States

Related Subject Headings

  • Zebrafish
  • Vesicular Transport Proteins
  • Vertebrates
  • Protein Transport
  • Protein Processing, Post-Translational
  • Protein Conformation
  • Organelles
  • Humans
  • Glycosylation
  • Disease Models, Animal
 

Citation

APA
Chicago
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Cox, N. J., Unlu, G., Bisnett, B. J., Meister, T. R., Condon, B. M., Luo, P. M., … Boyce, M. (2018). Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. Biochemistry, 57(1), 91–107. https://doi.org/10.1021/acs.biochem.7b00870
Cox, Nathan J., Gokhan Unlu, Brittany J. Bisnett, Thomas R. Meister, Brett M. Condon, Peter M. Luo, Timothy J. Smith, et al. “Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway.Biochemistry 57, no. 1 (January 9, 2018): 91–107. https://doi.org/10.1021/acs.biochem.7b00870.
Cox NJ, Unlu G, Bisnett BJ, Meister TR, Condon BM, Luo PM, et al. Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. Biochemistry. 2018 Jan 9;57(1):91–107.
Cox, Nathan J., et al. “Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway.Biochemistry, vol. 57, no. 1, Jan. 2018, pp. 91–107. Pubmed, doi:10.1021/acs.biochem.7b00870.
Cox NJ, Unlu G, Bisnett BJ, Meister TR, Condon BM, Luo PM, Smith TJ, Hanna M, Chhetri A, Soderblom EJ, Audhya A, Knapik EW, Boyce M. Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway. Biochemistry. 2018 Jan 9;57(1):91–107.
Journal cover image

Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

January 9, 2018

Volume

57

Issue

1

Start / End Page

91 / 107

Location

United States

Related Subject Headings

  • Zebrafish
  • Vesicular Transport Proteins
  • Vertebrates
  • Protein Transport
  • Protein Processing, Post-Translational
  • Protein Conformation
  • Organelles
  • Humans
  • Glycosylation
  • Disease Models, Animal