Occludin is required for apoptosis when claudin-claudin interactions are disrupted.

Cell Death & Disease
Neal E BeemanHeidi K Baumgartner

Abstract

Disruption of tight junctions is often seen during pathogen infection, inflammation, and tumor progression. Mislocalization of the tight junction proteins occludin and claudin in mammary epithelial monolayers leads to apoptosis through the extrinsic pathway. To further investigate the mechanism of this response, a normal mammary epithelial cell line (EpH4) as well as primary mammary epithelial cells were treated with a claudin-disrupting mimic peptide, DFYNP (aspartic acid-phenylalanine-tyrosine-asparagine-proline). Using fluorescent indicators, we found that caspase-3 activation, resulting from treatment with DFYNP, was restricted to EpH4 and primary mammary epithelial cells with mislocalized claudin-4. Mislocalized claudin-4 and occludin were colocalized in non-junctional puncta, and both molecules were found in the death-inducing signaling complex (DISC) where they colocalized with Fas, fas-associated protein with death domain (FADD), active caspase-8 and caspase-3 at distinct apical domains. Importantly, caspase-3 activation was totally repressed in primary mammary epithelial cells from occludin null mice. Thus, the apoptotic response appears to be initiated by the movement of occludin to the DISC suggesting that this molec...Continue Reading

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Citations

Mar 26, 2013·BMC Cell Biology·Patricia G WebbHeidi K Baumgartner
Nov 20, 2013·Journal of Mammary Gland Biology and Neoplasia·Kerst Stelwagen, Kuljeet Singh
Oct 18, 2012·Annual Review of Physiology·Michael Koval
Dec 19, 2015·Journal of Proteome Research·Fei LiuMark S Baker
Feb 24, 2016·Journal of Clinical Medicine·Yang Yu, Randolph C Elble
Sep 2, 2016·Tissue Barriers·Olga J Baker
Jun 8, 2012·Annals of the New York Academy of Sciences·Christian E OvergaardMichael Koval
Mar 26, 2014·Tissue Barriers·Christina M Van Itallie, James Melvin Anderson
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Sep 12, 2015·Endocrine Reviews·Dolores D Mruk, C Yan Cheng
Jun 5, 2019·Tissue Barriers·Jan F RichterJuliane Reiche
Dec 18, 2017·Turkish Journal of Biology = Türk Biyoloji Dergisi·Mostafa NajafiNematollah Gheibi
Feb 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Tao ZhouPengfei Lu
Dec 17, 2016·Experimental Lung Research·Felix R JimenezPaul R Reynolds
Apr 14, 2017·World Journal of Gastroenterology : WJG·Hanne Van SpaendonkBenedicte Y De Winter
Jul 7, 2017·Breast Cancer Research and Treatment·Marine GeoffroySandra Kuntz
Nov 6, 2018·Thorax·Raquel HerreroJosé Ángel Lorente
Nov 23, 2019·Iranian Journal of Pathology·Pouri SalehiKambiz Kamyab Hesari

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis