ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions.
ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions.
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作者：
组织屏障的形成和维持需要细胞力学和细胞-细胞连接组装的协调。在这里，我们结合了调节ECM刚度和测量粘附复合物的机械力的方法，以研究紧密连接如何调节细胞力学和上皮形态发生。我们发现紧密连接接头ZO-1的耗竭以ECM刚度依赖的方式破坏了连接组装和形态发生，并导致活性肌球蛋白的刚度依赖重组。通过抑制肌动球蛋白的收缩性，挽救了连接的形成和形态发生。ZO-1耗竭也影响了细胞-基质和e -钙粘蛋白基细胞-细胞粘附的机械张力。对e -钙粘蛋白的影响也取决于ECM刚度，并与ECM刚度对肌动蛋白细胞骨架组织的影响相关。然而，敲除ZO-1也揭示了ZO-1的张力无关功能。缺乏zo -1的细胞可以在低张力下组装功能屏障，但它们的紧密连接仍然被破坏，连接成分强烈减少和不连续募集。因此，我们的研究结果表明，ZO-1和细胞力学之间的相互调节控制着紧密连接的组装和上皮的形态发生，并且，在第二步，张力无关的步骤中，ZO-1需要在形态和结构上组装完全组装和功能正常的紧密连接。
Formation and maintenance of tissue barriers require the coordination of cell mechanics and cell–cell junction assembly. Here, we combined methods to modulate ECM stiffness and to measure mechanical forces on adhesion complexes to investigate how tight junctions regulate cell mechanics and epithelial morphogenesis. We found that depletion of the tight junction adaptor ZO-1 disrupted junction assembly and morphogenesis in an ECM stiffness-dependent manner and led to a stiffness-dependant reorganisation of active myosin. Both junction formation and morphogenesis were rescued by inhibition of actomyosin contractility. ZO-1 depletion also impacted mechanical tension at cell-matrix and E-cadherin-based cell–cell adhesions. The effect on E-cadherin also depended on ECM stiffness and correlated with effects of ECM stiffness on actin cytoskeleton organisation. However, ZO-1 knockout also revealed tension-independent functions of ZO-1. ZO-1-deficient cells could assemble functional barriers at low tension, but their tight junctions remained corrupted with strongly reduced and discontinuous recruitment of junctional components. Our results thus reveal that reciprocal regulation between ZO-1 and cell mechanics controls tight junction assembly and epithelial morphogenesis, and that, in a second, tension-independent step, ZO-1 is required to assemble morphologically and structurally fully assembled and functionally normal tight junctions.
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影响因子：
2.4
作者：
Calderón, V;Lázaro, A;Cereijido, M
通讯作者：
Cereijido, M
影响因子：
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作者：
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MARTINEZPALOMO, A
影响因子：
3.3
作者：
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通讯作者：
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通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
通讯作者：
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影响因子：
112.7
作者：
Iskratsch, Thomas;Wolfenson, Haguy;Sheetz, Michael P.
通讯作者：
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