Monster Jooske L, Donker Lisa, Vliem Marjolein J, Win Zaw, Matthews Helen K, Cheah Joleen S, Yamada Soichiro, de Rooij Johan, Baum Buzz, Gloerich Martijn
Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK.
J Cell Biol. 2021 May 3;220(5). doi: 10.1083/jcb.202001042.
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.
上皮组织不断进行自我更新，但在细胞有丝分裂过程中发生形态变化时，上皮组织的完整性是如何维持的，目前还不太清楚。在这里，我们表明，上皮细胞在进入有丝分裂时变圆，会对相邻细胞施加拉力。我们发现，有丝分裂期的细胞间连接通过肌动蛋白结合蛋白纽蛋白向基于钙黏蛋白的黏附位点进行机械敏感性募集来承受这些拉力。令人惊讶的是，募集到有丝分裂期连接的纽蛋白选择性地来源于有丝分裂细胞的邻居，导致钙黏蛋白连接的不对称组成。抑制有丝分裂细胞邻居中连接纽蛋白的募集会导致连接断裂和上皮屏障减弱。相反，有丝分裂细胞中钙黏蛋白复合物缺乏纽蛋白是成功进行有丝分裂变圆所必需的。因此，我们的数据确定了有丝分裂期间钙黏蛋白黏附处的不对称机械反应，这对于维持上皮组织的完整性同时使有丝分裂细胞发生形态变化至关重要。
