The mechanotransduction machinery at work at adherens junctions.
The mechanotransduction machinery at work at adherens junctions.
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DOI：
10.1039/c5ib00070j
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Mège RM
中科院分区：
文献类型：
--
作者：
Ladoux B;Nelson WJ;Yan J;Mège RM
多细胞体的形成以及成年组织的维持和修复需要微调细胞黏附反应以及细胞、其邻近细胞和基础细胞外基质之间的机械负荷传递。越来越多的研究领域集中在单个细胞如何感知其微环境(细胞外基质和其他细胞)的力学性质，以及机械转导途径如何影响细胞的形状、迁移、存活和分化。在多细胞组件中，由环境的物理属性施加的机械载荷被传递给邻近的细胞。细胞-细胞接触力不平衡导致细胞-细胞连接重塑、细胞极化和迁移、细胞挤出和细胞嵌入等基本的形态发生过程。然而，细胞如何响应和适应邻近细胞的机械特性，传递力，并将机械信号转换为化学信号仍然是悬而未决的问题。致密组织的一个明显特征是细胞之间在专门的粘连连接(AJ)上的粘连，涉及钙离子依赖的细胞-细胞粘连蛋白超家族(例如，上皮中的E-钙粘蛋白)。钙粘附素与细胞质蛋白β-catenin结合，后者又与丝状(F)-肌动蛋白结合接头蛋白α-catenin结合，后者也能募集纽蛋白，使细胞-细胞黏附蛋白与收缩的肌球蛋白细胞骨架之间建立机械连接。钙粘附素-连环蛋白黏附复合体是AJ的关键成分，对细胞组装的稳定性和细胞的动态运动起着重要作用。它也已经成为上皮性组织和非上皮性组织中力量传播的主要途径。在这里，我们讨论了最近的分子研究，指向α-连环蛋白的力依赖的构象变化，调节钙粘连蛋白-连环蛋白黏附复合体中的蛋白质相互作用，并表明α-连环蛋白是允许细胞局部感知、转导和适应环境机械约束的核心机械传感器。
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 mechanotranduction 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 Ca2+-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 constrain.