The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Occludin Phosphorylation and Ubiquitination Regulate Tight Junction Trafficking and Vascular Endothelial Growth Factor-induced Permeability
Open accessAbstract
Vascular endothelial growth factor (VEGF) alters tight junctions (TJs) and promotes vascular permeability in many retinal and brain diseases. However, the molecular mechanisms of barrier regulation are poorly understood. Here we demonstrate that occludin phosphorylation and ubiquitination regulate VEGF-induced TJ protein trafficking and concomitant vascular permeability. VEGF treatment induced TJ fragmentation and occludin trafficking from the cell border to early and late endosomes, concomitant with increased occludin phosphorylation on Ser-490 and ubiquitination. Furthermore, both co-immunoprecipitation and immunocytochemistry demonstrated that VEGF treatment increased the interaction between occludin and modulators of intracellular trafficking that contain the ubiquitin interacting motif, including Epsin-1, epidermal growth factor receptor pathway substrate 15 (Eps15), and hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs). Inhibiting occludin phosphorylation by mutating Ser-490 to Ala suppressed VEGF-induced ubiquitination, inhibited trafficking of TJ proteins, and prevented the increase in endothelial permeability. In addition, an occludin-ubiquitin chimera disrupted TJs and increased permeability without VEGF. These data demonstrate a novel mechanism of VEGF-induced occludin phosphorylation and ubiquitination that contributes to TJ trafficking and subsequent vascular permeability.
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Cites
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Occludin: a novel integral membrane protein localizing at tight junctions.
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Complex Phenotype of Mice Lacking Occludin, a Component of Tight Junction Strands
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Cited by
Antonetti, D. A., Klein, R., & Gardner, T. W. (2012) · New England Journal of Medicine · doi:10.1056/nejmra1005073 · Cited by 1,659
Self-citationBlood-brain barrier dysfunction and recovery after ischemic stroke
Jiang, X., Andjelkovic, A. V., Zhu, L., Yang, T., Bennett, M. V. L., Chen, J., Keep, R. F., & Shi, Y. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.10.001 · Cited by 936
Klaassen, I., Van Noorden, C. J. F., & Schlingemann, R. O. (2013) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2013.02.001 · Cited by 722
Tight Junction Structure and Function Revisited
Otani, T., & Furuse, M. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.08.004 · Cited by 665
Tight junction proteins occludin and ZO‐1 as regulators of epithelial proliferation and survival
Kuo, W., Odenwald, M. A., Turner, J. R., & Zuo, L. (2022) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14798 · Cited by 616
Metadata
- Authors
- Murakami, T., Felinski, E. A., & Antonetti, D. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 284
- Issue
- 31
- Pages
- 21036-21046
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2041225773
- Cited by
- 372
- References
- 51
- FWCI
- 11.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Occludin Phosphorylation and Ubiquitination Regulate Tight Junction Trafficking and Vascular Endothelial Growth Factor-induced Permeability. https://app.cochat.ai/papers/10.1074/jbc.m109.016766
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- Murakami, T., Felinski, E. A., & Antonetti, D. A. (2009). Occludin Phosphorylation and Ubiquitination Regulate Tight Junction Trafficking and Vascular Endothelial Growth Factor-induced Permeability. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.016766
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