Research

A key claudin extracellular loop domain is critical for epithelial barrier integrity


Reference:

Mrsny, R. J., Brown, G. T., Gerner-Smidt, K., Buret, A. G., Meddings, J. B., Quan, C., Koval, M. and Nusrat, A., 2008. A key claudin extracellular loop domain is critical for epithelial barrier integrity. American Journal Of Pathology, 172 (4), pp. 905-915.

Related documents:

This repository does not currently have the full-text of this item.
You may be able to access a copy if URLs are provided below. (Contact Author)

Official URL:

http://dx.doi.org/10.2353/ajpath.2008.070698

Abstract

Intercellular tight junctions (TJs) regulate epithelial barrier properties. Claudius are major structural constituents of TJs and belong to a large family of tetraspanning membrane proteins that have two predicted extracellular loops (ELs). Given that claudin-1 is widely expressed in epithelia, we further defined the role of its EL domains in determining TJ function. The effects of several claudin-1 EL mimetic peptides on epithelial barrier structure and function were examined. incubation of model human intestinal epithelial cells with a 27-amino acid peptide corresponding to a portion of the first EL domain (Cldn-1(53-80)) reversibly interfered with epithelial barrier function by inducing the rearrangement of key TJ proteins: occludin, claudin-1, junctional adhesion molecule-A, and zonula occludens-1. Cldn-1(53-80) associated with both claudin-1 and occludin, suggesting both the direct interference with the ability of these proteins to assemble into functional TJs and their close interaction under physiological conditions. These effects were specific for Cldn-1(53-80), because peptides corresponding to other claudin-1 EL domains failed to influence TJ function. Furthermore, the oral administration of Cldn-1(53-80) to rats increased paracellular gastric permeability. Thus, the identification of a critical claudin-1 EL motif, Cldn-1(53-80), capable of regulating TJ structure and function, offers a useful adjunct to treatments that require drug delivery across an epithelial barrier.

Details

Item Type Articles
CreatorsMrsny, R. J., Brown, G. T., Gerner-Smidt, K., Buret, A. G., Meddings, J. B., Quan, C., Koval, M. and Nusrat, A.
DOI10.2353/ajpath.2008.070698
DepartmentsFaculty of Science > Pharmacy & Pharmacology
RefereedYes
StatusPublished
ID Code20027

Export

Actions (login required)

View Item