Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells

Guan, Yanfang, Watson, Alastair J M ORCID:, Marchiando, Amanda M, Bradford, Emily, Shen, Le, Turner, Jerrold R and Montrose, Marshall H (2011) Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells. American Journal of Physiology - Cell Physiology, 300 (6). C1404-1414.

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We questioned how tight junctions contribute to intestinal barrier function during the cell shedding that is part of physiological cell renewal. Intravital confocal microscopy studied the jejunal villus epithelium of mice expressing a fluorescent zonula occludens 1 (ZO-1) fusion protein. Vital staining also visualized the cell nucleus (Hoechst staining) or local permeability to luminal constituents (Lucifer Yellow; LY). In a cell fated to be shed, ZO-1 redistributes from the tight junction toward the apical and then basolateral cell region. ZO-1 rearrangement occurs 15 ± 6 min (n = 28) before movement of the cell nucleus from the epithelial layer. During cell extrusion, permeation of luminal LY extends along the lateral intercellular spaces of the shedding cell only as far as the location of ZO-1. Within 3 min after detachment from the epithelial layer, nuclear chromatin condenses. After cell loss, a residual patch of ZO-1 remains in the space previously occupied by the departed cell, and the size of the patch shrinks to 14 ± 2% (n = 15) of the original cell space over 20 min. The duration of cell shedding measured by nucleus movement (14 ± 1 min) is much less than the total duration of ZO-1 redistribution at the same sites (45 ± 2 min). In about 15% of cell shedding cases, neighboring epithelial cells also undergo extrusion with a delay of 5-10 min. With the use of normal mice, ZO-1 immunofluorescent staining of fixed tissue confirmed ZO-1 redistribution and the presence of ZO-1 patches beneath shedding cells. Immunostaining also showed that redistribution of ZO-1 occurred without corresponding mixing of apical and basolateral membrane domains as marked by ezrin or E-cadherin. ZO-1 redistribution is the earliest cellular event yet identified as a herald of physiological cell shedding, and redistribution of tight junction function along the lateral plasma membrane sustains epithelial barrier during cell shedding.

Item Type: Article
Uncontrolled Keywords: animals,epithelial cells,intestinal mucosa,membrane proteins,mice,mice, inbred c57bl,mice, transgenic,phosphoproteins,recombinant fusion proteins,tight junctions,zonula occludens-1 protein
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Pure Connector
Date Deposited: 07 Jul 2014 14:02
Last Modified: 21 Aug 2023 00:25
DOI: 10.1152/ajpcell.00270.2010

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