Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Mol Biol Cell. 2019 Oct 1;30(21):2639-2650. doi: 10.1091/mbc.E19-04-0216. Epub 2019 Sep 4.
The adherens junction (AJ) couples the actin cytoskeletons of neighboring cells to allow mechanical integration and tissue organization. The physiological demands of intercellular adhesion require that the AJ be responsive to dynamic changes in force while maintaining mechanical load. These demands are tested in the heart, where cardiomyocyte AJs must withstand repeated cycles of actomyosin-mediated contractile force. Here we show that force-responsive cardiomyocyte AJs recruit actin-binding ligands to selectively couple actin networks. We employed a panel of N-cadherin-αE-catenin fusion proteins to rebuild AJs with specific actin linkages in N-cadherin-null cardiomyocytes. In this system, vinculin recruitment was required to rescue myofibril integration at nascent contacts. In contrast, loss of vinculin from the AJ disrupted junction morphology and blocked myofibril integration at cell-cell contacts. Our results identify vinculin as a critical link to contractile actomyosin and offer insight to how actin integration at the AJ is regulated to provide stability under mechanical load.
黏着连接（AJ）将相邻细胞的肌动蛋白细胞骨架连接起来，以实现机械整合和组织构建。细胞间黏附的生理需求要求 AJ 能够响应力的动态变化，同时保持机械负荷。在心脏中，这些需求会受到考验，心肌细胞 AJ 必须承受肌球蛋白介导的收缩力的反复循环。在这里，我们发现对力有反应的心肌细胞 AJ 会募集肌动蛋白结合配体，以选择性地连接肌动蛋白网络。我们使用了一组 N-钙黏蛋白-αE-连环蛋白融合蛋白，在 N-钙黏蛋白缺失的心肌细胞中重建具有特定肌动蛋白连接的 AJ。在这个系统中，黏着斑蛋白的募集对于在新生接触处拯救肌原纤维整合是必需的。相比之下，黏着斑蛋白从 AJ 中的缺失会破坏连接形态，并阻止肌原纤维在细胞-细胞连接处的整合。我们的结果确定了黏着斑蛋白作为与收缩性肌动球蛋白的关键连接，并提供了对 AJ 处肌动蛋白整合如何受到调节以在机械负荷下提供稳定性的深入了解。
