Vinculin anchors contractile actin to the cardiomyocyte adherens junction.
Vinculin anchors contractile actin to the cardiomyocyte adherens junction.
复制标题
纽蛋白将收缩肌动蛋白锚定到心肌细胞粘附连接处。
DOI：
10.1091/mbc.e19-04-0216
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发表时间：
2019
影响因子：
3.3
通讯作者：
Kwiatkowski,AdamV
中科院分区：
文献类型：
--
作者：
Merkel,ChelseaD;Li,Yang;Raza,Qanber;Stolz,DonnaB;Kwiatkowski,AdamV
粘附结（AJ）与邻近细胞的肌动蛋白细胞骨架偶联，以实现机械整合和组织组织。细胞间粘附的生理需求要求AJ在保持机械负荷的同时对力的动态变化做出反应。这些需求在心脏中进行了测试，其中心肌细胞AJs必须承受肌动球蛋白介导的收缩力的反复循环。在这里，我们表明力反应性心肌细胞AJs招募肌动蛋白结合配体选择性偶联肌动蛋白网络。我们使用一组N-cadherin-α - e -catenin融合蛋白在N-cadherin缺失的心肌细胞中重建具有特异性肌动蛋白连接的AJs。在这个系统中，需要招募血管蛋白来挽救新生接触时的肌原纤维整合。相反，AJ中血管蛋白的缺失破坏了连接形态，阻断了肌原纤维在细胞-细胞接触处的整合。我们的研究结果确定了血管蛋白是收缩肌动球蛋白的关键环节，并提供了如何调节AJ的肌动蛋白整合以在机械负荷下提供稳定性的见解。
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.