Disruption of occludin function in polarized epithelial cells activates the extrinsic pathway of apoptosis leading to cell extrusion without loss of transepithelial resistanceReport as inadecuate




Disruption of occludin function in polarized epithelial cells activates the extrinsic pathway of apoptosis leading to cell extrusion without loss of transepithelial resistance - Download this document for free, or read online. Document in PDF available to download.

BMC Cell Biology

, 10:85

First Online: 09 December 2009Received: 16 June 2009Accepted: 09 December 2009

Abstract

BackgroundOccludin is a tetraspanin protein normally localized to tight junctions. The protein interacts with a variety of pathogens including viruses and bacteria, an interaction that sometimes leads to its extrajunctional localization.

ResultsHere we report that treatment of mammary epithelial monolayers with a circularized peptide containing a four amino acid sequence found in the second extracellular loop of occludin, LHYH, leads to the appearance of extrajunctional occludin and activation of the extrinsic apoptotic pathway. At early times after peptide treatment endogenous occludin and the LYHY peptide were co-localized in extrajunctional patches, which were also shown to contain components of the death inducing signaling complex DISC, caspases 8 and 3, the death receptor FAS and the adaptor molecule FADD. After this treatment occludin could be immunoprecipitated with FADD, confirming its interaction with the DISC. Extrusion after LYHY treatment was accomplished with no loss of epithelial resistance.

ConclusionThese observations provide strong evidence that, following disruption, occludin forms a complex with the extrinsic death receptor leading to extrusion of apoptotic cells from the epithelial monolayer. They suggest that occludin has a protective as well as a barrier forming role in epithelia; pathogenic agents which utilize this protein as an entry point into the cell might set off an apoptotic reaction allowing extrusion of the infected cell before the pathogen can gain entry to the interstitial space.

AbbreviationsAd-FΔOcc

N-terminally FLAG taggedN-terminally truncated mouse occludin mutant

BAPbacterial alkaline phosphatase

DISCDeath inducing signaling complex

EPECenteropathogenic Escherichia coli

GFPgreen fluorescent protein

TERtransepithelial resistance

TUNELTerminal deoxynucleotidyl transferase dUTP nick end labeling.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-10-85 contains supplementary material, which is available to authorized users.

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Author: Neal E Beeman - Heidi K Baumgartner - Patricia G Webb - Jerome B Schaack - Margaret C Neville

Source: https://link.springer.com/article/10.1186/1471-2121-10-85



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