Mechanism of the cadherin-catenin F-actin catch bond interaction.
Mechanism of the cadherin-catenin F-actin catch bond interaction.
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DOI：
10.7554/elife.80130
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发表时间：
2022-08-01
期刊：
影响因子：
7.7
通讯作者：
Weis, William, I
中科院分区：
文献类型：
--
作者：
Wang, Amy;Dunn, Alexander R.;Weis, William, I
细胞-细胞粘附中的机械转导对于上皮的结构完整性、组织和形态发生至关重要。在细胞-细胞连接处，三元E-cadherin/β-catenin/αE-catenin复合物通过与F-actin结合来感知和传递机械载荷。与F-肌动蛋白的相互作用，被描述为一个两个状态的捕捉键，是弱的解决方案，但加强施加的力，由于弱和强肌动蛋白结合状态之间的力依赖性的转换。在这里，我们提供了直接的证据，从光学捕获实验，捕获键的性质主要存在于α E-连环蛋白肌动蛋白结合域（ABD）。与我们先前提出的模型一致，五螺旋ABD束的第一个螺旋的缺失使得能够在最小负载下与F-肌动蛋白稳定相互作用，这通过单态滑动键很好地描述，即使当α E-连环蛋白与β-连环蛋白和E-钙粘蛋白复合时。我们的数据表明，具有结构相似ABD的粘附蛋白具有保守的捕获键机制。我们还证明了一个稳定结合的ABD加强了相邻复合物和F-肌动蛋白之间的负载依赖性结合相互作用，但其他α E-连环蛋白结构域的存在削弱了这种作用。这些结果提供了机械的洞察力的钙粘蛋白-连环蛋白复合物的合作绑定F-肌动蛋白，调节动态细胞骨架连接上皮组织。
Mechanotransduction at cell–cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At cell–cell junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense and transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, is weak in solution but is strengthened by applied force due to force-dependent transitions between weak and strong actin-binding states. Here, we provide direct evidence from optical trapping experiments that the catch bond property principally resides in the αE-catenin actin-binding domain (ABD). Consistent with our previously proposed model, the deletion of the first helix of the five-helix ABD bundle enables stable interactions with F-actin under minimal load that are well described by a single-state slip bond, even when αE-catenin is complexed with β-catenin and E-cadherin. Our data argue for a conserved catch bond mechanism for adhesion proteins with structurally similar ABDs. We also demonstrate that a stably bound ABD strengthens load-dependent binding interactions between a neighboring complex and F-actin, but the presence of the other αE-catenin domains weakens this effect. These results provide mechanistic insight to the cooperative binding of the cadherin–catenin complex to F-actin, which regulate dynamic cytoskeletal linkages in epithelial tissues.