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Analysis of Occludin Trafficking, Demonstrating Continuous Endocytosis, Degradation, Recycling and Biosynthetic Secretory Trafficking
Open accessAbstract
Tight junctions (TJs) link adjacent cells and are critical for maintenance of apical-basolateral polarity in epithelial monolayers. The TJ protein occludin functions in disparate processes, including wound healing and Hepatitis C Virus infection. Little is known about steady-state occludin trafficking into and out of the plasma membrane. Therefore, we determined the mechanisms responsible for occludin turnover in confluent Madin-Darby canine kidney (MDCK) epithelial monolayers. Using various biotin-based trafficking assays we observed continuous and rapid endocytosis of plasma membrane localised occludin (the majority internalised within 30 minutes). By 120 minutes a significant reduction in internalised occludin was observed. Inhibition of lysosomal function attenuated the reduction in occludin signal post-endocytosis and promoted co-localisation with the late endocytic system. Using a similar method we demonstrated that ∼20% of internalised occludin was transported back to the cell surface. Consistent with these findings, significant co-localisation between internalised occludin and recycling endosomal compartments was observed. We then quantified the extent to which occludin synthesis and transport to the plasma membrane contributes to plasma membrane occludin homeostasis, identifying inhibition of protein synthesis led to decreased plasma membrane localised occludin. Significant co-localisation between occludin and the biosynthetic secretory pathway was demonstrated. Thus, under steady-state conditions occludin undergoes turnover via a continuous cycle of endocytosis, recycling and degradation, with degradation compensated for by biosynthetic exocytic trafficking. We developed a mathematical model to describe the endocytosis, recycling and degradation of occludin, utilising experimental data to provide quantitative estimates for the rates of these processes.
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Proper assembly and functioning of junctional proteins are channelized through exocytic transportation of newly synthesized proteins to the cell surface and recycling of mature tight junctions and adherens junctions via endocytosis.
“The proper assembly and functioning of junctional proteins are channelized through exocytic transportation of newly synthesized proteins to the cell surface and recycling of mature TJs and AJs via endocytosis [198].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [198]
The Abstract reports that occludin, a tight-junction protein, undergoes endocytosis and recycling, while biosynthetic exocytic trafficking replenishes it at the cell surface. The study concerns occludin in MDCK epithelial cells; it does not establish the same pathways for adherens junctions or show that they ensure proper junction assembly and function. (LLM, conf=0.87)
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Cites
An Adaptive Metropolis Algorithm
Haario, H., Saksman, E., & Tamminen, J. (2001) · Bernoulli · doi:10.2307/3318737 · Cited by 2,687
Haario, H., Laine, M., Mira, A., & Saksman, E. (2006) · Statistics and Computing · doi:10.1007/s11222-006-9438-0 · Cited by 1,503
Yoshimori, T., Yamamoto, A., Moriyama, Y., Futai, M., & Tashiro, Y. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47429-2 · Cited by 1,334
Rab11 regulates recycling through the pericentriolar recycling endosome.
Ullrich, O., Reinsch, S., Urbé, S., Zerial, M., & Parton, R. G. (1996) · The Journal of cell biology · doi:10.1083/jcb.135.4.913 · Cited by 1,197
Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin
Schneider‐Poetsch, T., Ju, J., Eyler, D. E., Dang, Y., Bhat, S., Merrick, W. C., Green, R., Shen, B., & Liu, J. O. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.304 · Cited by 1,050
Marchiando, A. M., Shen, L., Graham, W. V., Weber, C. R., Schwarz, B. T., Austin, J. R., Raleigh, D. R., Guan, Y., Watson, A. J. M., Montrose, M. H., et al. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200902153 · Cited by 475
Dynamics and functions of tight junctions
Steed, E., Balda, M. S., & Matter, K. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.12.002 · Cited by 418
Jaiswal, J. K., Andrews, N. W., & Simon, S. M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200208154 · Cited by 394
Caswell, P. T., Chan, M. T., Lindsay, A. J., McCaffrey, M., Boettiger, D. C., & Norman, J. C. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200804140 · Cited by 389
Ivanov, A. I., Nusrat, A., & Parkos, C. A. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-05-0319 · Cited by 385
Murakami, T., Felinski, E. A., & Antonetti, D. A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016766 · Cited by 369
Taraska, J. W., Perrais, D., Ohara‐Imaizumi, M., Nagamatsu, S., & Almers, W. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337526100 · Cited by 361
Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of β1-integrins
Pellinen, T. S., Arjonen, A., Vuoriluoto, K., Kallio, K., Fransen, J. A. M., & Ivaska, J. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200509019 · Cited by 343
Stamatovic, S. M., Keep, R. F., Wang, M. M., Janković, I., & Andjelkovic, A. V. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.000521 · Cited by 203
Traweger, A., Fang, D., Liu, Y., Stelzhammer, W., Krizbai, I. A., Fresser, F., Bauer, H. C., & Bauer, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111384200 · Cited by 199
Three-dimensional analysis of post-Golgi carrier exocytosis in epithelial cells
Kreitzer, G., Schmoranzer, J., Low, S. H., Li, X., Gan, Y., Weimbs, T., Simon, S. M., & Rodriguez-Boulan, E. (2003) · Nature Cell Biology · doi:10.1038/ncb917 · Cited by 196
Xia, W., Wong, E. W. P., Mruk, D. D., & Cheng, C. Y. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.11.028 · Cited by 179
The Tight Junction Protein, Occludin, Regulates the Directional Migration of Epithelial Cells
Du, D., Xu, F., Yu, L., Zhang, C., Lü, X., Yuan, H., Huang, Q., Zhang, F., Bao, H., Jia, L., et al. (2010) · Developmental Cell · doi:10.1016/j.devcel.2009.12.008 · Cited by 175
Fuller, S. D., & Simons, K. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.5.1767 · Cited by 175
Hepatitis C Virus Induces CD81 and Claudin-1 Endocytosis
Farquhar, M. J., Hu, K., Harris, H. J., Davis, C., Brimacombe, C. L., Fletcher, S. J., Baumert, T. F., Rappoport, J. Z., Balfe, P., & McKeating, J. A. (2012) · Journal of Virology · doi:10.1128/jvi.06996-11 · Cited by 148
Self-citationRab13 Mediates the Continuous Endocytic Recycling of Occludin to the Cell Surface
Morimoto, S., Nishimura, N., Terai, T., Manabe, S., Yamamoto, Y., Shinahara, W., Miyake, H., Tashiro, S., Shimada, M., & Sasaki, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406906200 · Cited by 146
Baravalle, G., Schober, D., Huber, M., Bayer, N., Murphy, R. F., & Fuchs, R. (2005) · Cell and Tissue Research · doi:10.1007/s00441-004-1060-x · Cited by 142
Epithelial cell polarity and disease
Wilson, P. D. (1997) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1997.272.4.f434 · Cited by 126
The Small GTPase Rab13 Regulates Assembly of Functional Tight Junctions in Epithelial Cells
Marzesco, A., Dunia, I., Pandjaitan, R., Recouvreur, M., Dauzonne, D., Benedetti, L. E., Louvard, D., & Zahraoui, A. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.02-02-0029 · Cited by 117
Hepatitis C virus entry: beyond receptors
Meredith, L. W., Wilson, G. K., Fletcher, N. F., & McKeating, J. A. (2012) · Reviews in Medical Virology · doi:10.1002/rmv.723 · Cited by 97
Stimulus-induced reorganization of tight junction structure: The role of membrane traffic
Yu, D., & Turner, J. R. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.07.027 · Cited by 93
Su, L., Mruk, D. D., Lee, W. M., & Cheng, C. Y. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.07.018 · Cited by 86
Harhaj, N. S., Barber, A. J., & Antonetti, D. A. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10183 · Cited by 72
Dukes, J. D., Fish, L. P., Richardson, J. D., Blaikley, E., Burns, S., Caunt, C. J., Chalmers, A. D., & Whitley, P. R. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-04-0343 · Cited by 67
Initial steps in receptor-mediated endocytosis
Goldenthal, K. L., Pastan, I. H., & Willingham, M. C. (1984) · Experimental Cell Research · doi:10.1016/0014-4827(84)90658-x · Cited by 59
Dukes, J. D., Whitley, P. R., & Chalmers, A. D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0028659 · Cited by 57
The second extracellular loop dictates Occludin-mediated HCV entry
Liu, S., Kuo, W., Yang, W. Z., Liu, W., Gibson, G. A., Dorko, K., Watkins, S. C., Strom, S. C., & Wang, T. (2010) · Virology · doi:10.1016/j.virol.2010.08.009 · Cited by 57
Fletcher, S. J., Poulter, N. S., Haining, E. J., & Rappoport, J. Z. (2011) · Biology of the Cell · doi:10.1111/boc.201100004 · Cited by 23
Self-citationLocalization and topology of a urate transporter/channel, a galectin, in epithelium-derived cells
Rappoport, J. Z., Lipkowitz, M. S., & Abramson, R. G. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.6.c1926 · Cited by 16
Self-citationHerman, D., Thomas, C. M., & Stekel, D. J. (2011) · BMC Systems Biology · doi:10.1186/1752-0509-5-119 · Cited by 14
Self-citation
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- S Morimoto, 2005, Rab13 mediates the continuous endocytic recycling of occludin to the cell surface, J Biol Chem, 280, 2220, 10.1074/jbc.m406906200 · DOI
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Endocytosis of tight junction proteins and the regulation of degradation and recycling
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Saha, K., Ganapathy, A. S., Wang, A., Morris, N. M., Suchanec, E., Ding, W. Y., Yochum, G. S., Koltun, W. A., Nighot, M., Ma, T., et al. (2022) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjac148 · Cited by 72
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Mitra, S., Federico, L., Zhao, W., Dennison, J. B., Sarkar, T. R., Zhang, F., Takiar, V., Cheng, K. W., Mani, S. A., Lee, J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9730 · Cited by 46
Nighot, P. K., Leung, L., & Ma, T. Y. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.01.024 · Cited by 39
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Metadata
- Authors
- Fletcher, S. J., Iqbal, M., Jabbari, S., Stekel, D., & Rappoport, J. Z.
- Affiliations
- University of Birmingham (GB)
- University of Nottingham (GB)
- Northwestern University (US)
- Corresponding author
- Fletcher, Sarah J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-11-25
- Volume
- 9
- Issue
- 11
- Pages
- e111176
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4244031
- OpenAlex
- W1987282988
- Cited by
- 25
- References
- 35
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 1
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Research Explorer (The University of Manchester) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Funders
- Advantage West Midlands
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- occludin, tight junctions, protein trafficking, endocytosis, protein degradation, recycling endosomes, lysosomes, protein turnover, mathematical model, MDCK cells, apical-basal polarity
- MeSH terms
- Animals, Dogs, Endocytosis, Protein Processing, Post-Translational, Tight Junctions, Protein Transport, Secretory Pathway, Proteolysis, Madin Darby Canine Kidney Cells, Occludin
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