Joy-Immediato Michelle, Ramirez Manuel J, Cerda Mauricio, Toyama Yusuke, Ravasio Andrea, Kanchanawong Pakorn, Bertocchi Cristina
Laboratory for Molecular Mechanics of Cell Adhesion, Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Front Cell Dev Biol. 2021 Jun 17;9:669086. doi: 10.3389/fcell.2021.669086. eCollection 2021.
Cadherin-mediated adhesions (also known as adherens junctions) are adhesive complexes that connect neighboring cells in a tissue. While the role of the actin cytoskeleton in withstanding tension at these sites of contact is well documented, little is known about the involvement of microtubules and the associated endoplasmic reticulum (ER) network in cadherin mechanotransduction. Therefore, we investigated how the organization of ER extensions in close proximity of cadherin-mediated adhesions can affect such complexes, and vice versa. Here, we show that the extension of the ER to cadherin-mediated adhesions is tension dependent and appears to be cadherin-type specific. Furthermore, the different structural organization of the ER/microtubule network seems to affect the localization of ER-bound PTP1B at cadherin-mediated adhesions. This phosphatase is involved in the modulation of vinculin, a molecular clutch which enables differential engagement of the cadherin-catenin layer with the actomyosin cytoskeleton in response to tension. This suggests a link between structural organization of the ER/microtubule network around cadherin-specific adhesions, to control the mechanotransduction of adherens junctions by modulation of vinculin conformational state.
钙黏蛋白介导的黏附（也称为黏着连接）是连接组织中相邻细胞的黏附复合体。虽然肌动蛋白细胞骨架在这些接触位点承受张力方面的作用已有充分记录，但关于微管及相关内质网（ER）网络在钙黏蛋白机械转导中的参与情况却知之甚少。因此，我们研究了紧邻钙黏蛋白介导的黏附处内质网延伸的组织方式如何影响此类复合体，反之亦然。在此，我们表明内质网向钙黏蛋白介导的黏附处的延伸是张力依赖性的，且似乎具有钙黏蛋白类型特异性。此外，内质网/微管网络的不同结构组织似乎会影响内质网结合的蛋白酪氨酸磷酸酶1B（PTP1B）在钙黏蛋白介导的黏附处的定位。这种磷酸酶参与纽蛋白的调节，纽蛋白是一种分子离合器，可使钙黏蛋白 - 连环蛋白层根据张力与肌动球蛋白细胞骨架进行差异结合。这表明钙黏蛋白特异性黏附周围内质网/微管网络的结构组织与通过调节纽蛋白构象状态来控制黏着连接的机械转导之间存在联系。
