ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation.
ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation.
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DOI：
10.1083/jcb.201404140
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发表时间：
2015-03-16
期刊：
影响因子：
--
通讯作者：
Balda MS
中科院分区：
文献类型：
--
作者：
Tornavaca O;Chia M;Dufton N;Almagro LO;Conway DE;Randi AM;Schwartz MA;Matter K;Balda MS
ZO-1调节VE-钙粘蛋白依赖的内皮连接和肌动球蛋白组织，从而影响细胞-细胞张力、迁移、血管生成和屏障形成细胞间连接对于机械转导至关重要，但紧密连接是否有助于调节细胞-细胞张力和粘附连接尚不清楚。在这里，我们证明了紧密连接蛋白ZO-1调节张力作用于VE-钙粘蛋白为基础的粘附连接，细胞迁移，原代内皮细胞的屏障形成，以及血管生成在体外和体内。ZO-1缺失导致紧密连接破坏，活性肌球蛋白II从连接处重新分布到应力纤维，VE-钙粘蛋白上的张力降低，连接机械传感器（如粘着斑蛋白和PAK 2）丢失，并诱导粘着斑蛋白从α-连环蛋白-VE-钙粘蛋白复合物中解离。Claudin-5耗竭仅模拟ZO-1对屏障形成的作用，而对机械转换器的作用通过抑制ROCK而被拯救，并通过JAM-A、JACOP或p114 RhoGEF下调而被表型模仿。ZO-1是JACOP的交界性募集所必需的，而JACOP反过来又募集p114 RhoGEF。因此，ZO-1是VE-钙粘蛋白依赖性内皮连接的中心调节因子，其协调空间肌动球蛋白组织，调节细胞-细胞张力、迁移、血管生成和屏障形成。
ZO-1 regulates VE-cadherin–dependent endothelial junctions and actomyosin organization, thereby influencing cell–cell tension, migration, angiogenesis, and barrier formation Intercellular junctions are crucial for mechanotransduction, but whether tight junctions contribute to the regulation of cell–cell tension and adherens junctions is unknown. Here, we demonstrate that the tight junction protein ZO-1 regulates tension acting on VE-cadherin–based adherens junctions, cell migration, and barrier formation of primary endothelial cells, as well as angiogenesis in vitro and in vivo. ZO-1 depletion led to tight junction disruption, redistribution of active myosin II from junctions to stress fibers, reduced tension on VE-cadherin and loss of junctional mechanotransducers such as vinculin and PAK2, and induced vinculin dissociation from the α-catenin–VE-cadherin complex. Claudin-5 depletion only mimicked ZO-1 effects on barrier formation, whereas the effects on mechanotransducers were rescued by inhibition of ROCK and phenocopied by JAM-A, JACOP, or p114RhoGEF down-regulation. ZO-1 was required for junctional recruitment of JACOP, which, in turn, recruited p114RhoGEF. ZO-1 is thus a central regulator of VE-cadherin–dependent endothelial junctions that orchestrates the spatial actomyosin organization, tuning cell–cell tension, migration, angiogenesis, and barrier formation.
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DOI：
10.1016/j.bbrc.2009.01.100
发表时间：
2009-03-06
影响因子：
3.1
作者：
Gutwein, Paul;Schramme, Anja;Pfeilschifter, Josef
通讯作者：
Pfeilschifter, Josef
影响因子：
7.8
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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DOI：
10.1111/j.1749-6632.2012.06506.x
发表时间：
2012-01-01
期刊：
BARRIERS AND CHANNELS FORMED BY TIGHT JUNCTION PROTEINS I
影响因子：
--
作者：
Citi, Sandra;Pulimeno, Pamela;Paschoud, Serge
通讯作者：
Paschoud, Serge
影响因子：
3.3
作者：
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通讯作者：
Tsukita, Sachiko