![]() Force-induced vinculin recruitment to the cadherin complex has been implicated in tissue integrity ( Huveneers et al., 2012) however, during which physiological processes this mechanoresponse is essential remains less well understood ( Chen et al., 2018 Pannekoek et al., 2019). Vinculin provides additional connections between the cadherin complex and actin and regulates local actin assembly ( Leerberg et al., 2014 Ito et al., 2017), which can stiffen and strengthen cadherin adhesions ( le Duc et al., 2010 Ladoux et al., 2010 Liu et al., 2010 Leckband et al., 2011). The best established among these is vinculin, which localizes to adherens junctions upon the tension-sensitive conformational opening of its binding site within α-catenin ( le Duc et al., 2010 Yonemura et al., 2010 Thomas et al., 2013 Yao et al., 2014). ![]() ![]() Moreover, the cadherin complex actively senses tensile forces between cells, which can trigger junctional reinforcement by recruitment of actin-modulating proteins that strengthen the cadherin-actin link ( Leckband and de Rooij, 2014 Mège and Ishiyama, 2017 Charras and Yap, 2018). The cytosolic tail of E-cadherin associates with F-actin through β- and α-catenin, thereby coupling neighboring cells and their actomyosin cytoskeletons ( Mège and Ishiyama, 2017). Integrity of the epithelial barrier depends on intercellular cohesion through adherens junctions, which are formed by homotypic interactions between E-cadherin proteins of adjacent cells. This barrier has to withstand the mechanical stresses to which epithelial cells are exposed, for instance, during morphogenetic movements ( Takeichi, 2014 Lecuit and Yap, 2015). 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.Įpithelia cover the body surface and organs to form a regulated barrier between the internal and external environment. Conversely, the absence of vinculin from the cadherin complex in mitotic cells is necessary to successfully undergo mitotic rounding. Inhibition of junctional vinculin recruitment in neighbors of mitotic cells results in junctional breakage and weakened epithelial barrier. Surprisingly, vinculin that is recruited to mitotic junctions originates selectively from the neighbors of mitotic cells, resulting in an asymmetric composition of cadherin junctions. 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. Here, we show that as epithelial cells round up when they enter mitosis, they exert tensile forces on neighboring cells. Epithelia are continuously self-renewed, but how epithelial integrity is maintained during the morphological changes that cells undergo in mitosis is not well understood.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |