An asymmetric junctional mechanoresponse coordinates mitotic rounding with epithelial integrity |
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| Authors: | Jooske L. Monster Lisa Donker Marjolein J. Vliem Zaw Win Helen K. Matthews Joleen S. Cheah Soichiro Yamada Johan de Rooij Buzz Baum Martijn Gloerich |
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| Affiliation: | 1.Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands;2.Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK;3.Department of Biomedical Engineering, University of California, Davis, Davis, CA |
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| Abstract: | Epithelia are continuously self-renewed, but how epithelial integrity is maintained during the morphological changes that cells undergo in mitosis is not well understood. Here, we show that as epithelial cells round up when they enter mitosis, they exert tensile forces on neighboring cells. We find that mitotic cell–cell junctions withstand these tensile forces through the mechanosensitive recruitment of the actin-binding protein vinculin to cadherin-based adhesions. Surprisingly, vinculin that is recruited to mitotic junctions originates selectively from the neighbors of mitotic cells, resulting in an asymmetric composition of cadherin junctions. Inhibition of junctional vinculin recruitment in neighbors of mitotic cells results in junctional breakage and weakened epithelial barrier. Conversely, the absence of vinculin from the cadherin complex in mitotic cells is necessary to successfully undergo mitotic rounding. Our data thus identify an asymmetric mechanoresponse at cadherin adhesions during mitosis, which is essential to maintain epithelial integrity while at the same time enable the shape changes of mitotic cells. |
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