Ladoux B, Nelson W J, Yan J, Mège R M
Institut Jacques Monod, CNRS, Université Paris Diderot, Paris, France.
Integr Biol (Camb). 2015 Oct;7(10):1109-19. doi: 10.1039/c5ib00070j. Epub 2015 May 13.
The shaping of a multicellular body, and the maintenance and repair of adult tissues require fine-tuning of cell adhesion responses and the transmission of mechanical load between the cell, its neighbors and the underlying extracellular matrix. A growing field of research is focused on how single cells sense mechanical properties of their micro-environment (extracellular matrix, other cells), and on how mechanotransduction pathways affect cell shape, migration, survival as well as differentiation. Within multicellular assemblies, the mechanical load imposed by the physical properties of the environment is transmitted to neighboring cells. Force imbalance at cell-cell contacts induces essential morphogenetic processes such as cell-cell junction remodeling, cell polarization and migration, cell extrusion and cell intercalation. However, how cells respond and adapt to the mechanical properties of neighboring cells, transmit forces, and transform mechanical signals into chemical signals remain open questions. A defining feature of compact tissues is adhesion between cells at the specialized adherens junction (AJ) involving the cadherin super-family of Ca(2+)-dependent cell-cell adhesion proteins (e.g., E-cadherin in epithelia). Cadherins bind to the cytoplasmic protein β-catenin, which in turn binds to the filamentous (F)-actin binding adaptor protein α-catenin, which can also recruit vinculin, making the mechanical connection between cell-cell adhesion proteins and the contractile actomyosin cytoskeleton. The cadherin-catenin adhesion complex is a key component of the AJ, and contributes to cell assembly stability and dynamic cell movements. It has also emerged as the main route of propagation of forces within epithelial and non-epithelial tissues. Here, we discuss recent molecular studies that point toward force-dependent conformational changes in α-catenin that regulate protein interactions in the cadherin-catenin adhesion complex, and show that α-catenin is the core mechanosensor that allows cells to locally sense, transduce and adapt to environmental mechanical constrains.
多细胞生物体的形成以及成体组织的维持和修复需要对细胞黏附反应进行微调，并在细胞与其邻居以及下方的细胞外基质之间传递机械负荷。一个不断发展的研究领域聚焦于单个细胞如何感知其微环境（细胞外基质、其他细胞）的机械特性，以及机械转导途径如何影响细胞形状、迁移、存活和分化。在多细胞聚集体中，由环境物理特性施加的机械负荷会传递给相邻细胞。细胞间接触处的力不平衡会引发诸如细胞间连接重塑、细胞极化和迁移、细胞挤出和细胞插入等重要的形态发生过程。然而，细胞如何响应并适应相邻细胞的机械特性、传递力以及将机械信号转化为化学信号仍然是悬而未决的问题。致密组织的一个决定性特征是在涉及钙黏蛋白超家族的Ca(2+)依赖性细胞间黏附蛋白（例如上皮细胞中的E-钙黏蛋白）的特化黏着连接（AJ）处细胞之间的黏附。钙黏蛋白与细胞质蛋白β-连环蛋白结合，β-连环蛋白又与丝状（F）-肌动蛋白结合衔接蛋白α-连环蛋白结合，α-连环蛋白还可以募集纽蛋白，从而在细胞间黏附蛋白和收缩性肌动球蛋白细胞骨架之间建立机械连接。钙黏蛋白-连环蛋白黏附复合体是AJ的关键组成部分，有助于细胞组装的稳定性和细胞的动态运动。它也已成为上皮组织和非上皮组织中力传播的主要途径。在这里，我们讨论了最近的分子研究，这些研究指出α-连环蛋白中依赖力的构象变化调节了钙黏蛋白-连环蛋白黏附复合体中的蛋白质相互作用，并表明α-连环蛋白是核心机械传感器，使细胞能够局部感知、转导并适应环境机械约束。
