Synaptopodin couples epithelial contractility to α-actinin-4-dependent junction maturation
Synaptopodin couples epithelial contractility to α-actinin-4-dependent junction maturation
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DOI：
10.1083/jcb.201412003
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发表时间：
2015-10-26
影响因子：
7.8
通讯作者：
Tang, Vivian W.
中科院分区：
文献类型：
--
作者：
Kannan, Nivetha;Tang, Vivian W.
上皮连接经历由内源性肌动球蛋白活性和与邻近细胞的相互作用施加的机械力。我们假设细胞间粘附接触产生的张力有助于连接复合体的成熟和组装。为了验证我们的假设，我们使用了一个液压装置，可以施加机械力的细胞间连接在一个汇合的单层细胞。我们发现，机械力诱导α-辅肌动蛋白-4和肌动蛋白积累在细胞连接在一个时间和张力依赖性的方式在连接发展。细胞间张力还诱导黏着斑蛋白向细胞连接的α-辅肌动蛋白-A依赖性募集。此外，我们已经确定了一个张力敏感的上游调节α-辅肌动蛋白-4作为synaptopodin。突触足蛋白形成含有α-辅肌动蛋白-4和β-连环蛋白的复合物，并与肌球蛋白II相互作用，表明它可以将粘附分子物理连接到细胞收缩装置。突触足蛋白耗竭阻止α-辅肌动蛋白-4、粘着斑蛋白和肌动蛋白的连接积聚。突触足蛋白和α-辅肌动蛋白-4的敲低降低了细胞-细胞粘附的强度，降低了单层通透性屏障，并损害了细胞收缩性。我们的研究结果强调了连接发展的复杂性，并暗示了通过紧张诱导的连接组件的顺序纳入控制过程。
The epithelial junction experiences mechanical force exerted by endogenous actomyosin activities and from interactions with neighboring cells. We hypothesize that tension generated at cell-cell adhesive contacts contributes to the maturation and assembly of the junctional complex. To test our hypothesis, we used a hydraulic apparatus that can apply mechanical force to intercellular junction in a confluent monolayer of cells. We found that mechanical force induces alpha-actinin-4 and actin accumulation at the cell junction in a time- and tension-dependent manner during junction development. Intercellular tension also induces alpha-actinin-A dependent recruitment of vinculin to the cell junction. In addition, we have identified a tension-sensitive upstream regulator of alpha-actinin-4 as synaptopodin. Synaptopodin forms a complex containing alpha-actinin-4 and beta-catenin and interacts with myosin II, indicating that it can physically link adhesion molecules to the cellular contractile apparatus. Synaptopodin depletion prevents junctional accumulation of alpha-actinin-4, vinculin, and actin. Knockdown of synaptopodin and alpha-actinin-4 decreases the strength of cell-cell adhesion, reduces the monolayer permeability barrier, and compromises cellular contractility. Our findings underscore the complexity of junction development and implicate a control process via tension-induced sequential incorporation of junctional components.