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Author Notes:

Email: anusrat@emory.edu.

We thank David Lo for providing the pCMV-acGFP claudin 4 Caco-2 BBE cells, Noah Shroyer for assistance with enteroid cultures, and Oskar Laur at the Emory Cloning Core, Robert Karaffa at the Emory University Flow Cytometry Core Facility, and Mike Kwon, In-Fah Lee, and Jeff Vallance for expert technical assistance.

The authors have no conflicts of interest.


Research Funding:

Supported by the National Institutes of Health (DK64399 to C.A.P.; DK55679 and DK59888 to A.N.; HL116958 to M.K.; and DK64399 [National Institutes of Health DDRC grant]), Emory University Integrated Cellular Imaging Microscopy Core of the Winship Cancer Institute Comprehensive Cancer Center Grant P30CA138292, a Crohn's and Colitis Foundation of America Career Development award to C.T.C. and a fellowship award to A.E.F., and Deutsche Forschungsgemeinschaft FOR 721 TP-Z to S.M.K. and M.F.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology

Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins


Journal Title:

Molecular Biology of the Cell


Volume 25, Number 18


, Pages 2710-2719

Type of Work:

Article | Final Publisher PDF


Tight junctions (TJs) are dynamic, multiprotein intercellular adhesive contacts that provide a vital barrier function in epithelial tissues. TJs are remodeled during physiological development and pathological mucosal inflammation, and differential expression of the claudin family of TJ proteins determines epithelial barrier properties. However, the molecular mechanisms involved in TJ remodeling are incompletely understood. Using acGFP-claudin 4 as a biosensor of TJ remodeling, we observed increased claudin 4 fluorescence recovery after photobleaching (FRAP) dynamics in response to inflammatory cytokines. Interferon γ and tumor necrosis factor α increased the proportion of mobile claudin 4 in the TJ. Up-regulation of claudin 4 protein rescued these mobility defects and cytokine-induced barrier compromise. Furthermore, claudins 2 and 4 have reciprocal effects on epithelial barrier function, exhibit differential FRAP dynamics, and compete for residency within the TJ. These findings establish a model of TJs as self-assembling systems that undergo remodeling in response to proinflammatory cytokines through a mechanism of heterotypic claudin-binding incompatibility.

Copyright information:

© 2014 Capaldo et al.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License ( http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits making multiple copies, distribution, public display, and publicly performance, distribution of derivative works, provided the original work is properly cited. This license requires credit be given to copyright holder and/or author, derivative works be licensed under the same terms or compatible terms as the original work, copyright and license notices be kept intact. This license prohibits exercising rights for commercial purposes.

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