A key step in regulation of Hippo pathway signaling in response to mechanical tension is recruitment of the LIM domain proteins TRIP6 and LIMD1 to adherens junctions. Mechanical tension also triggers TRIP6 and LIMD1 to bind and inhibit the Hippo pathway kinase LATS1. How TRIP6 and LIMD1 are recruited to adherens junctions in response to tension is not clear, but previous studies suggested that they could be regulated by the known mechanosensory proteins α‐catenin and vinculin at adherens junctions. We found that the three LIM domains of TRIP6 and LIMD1 are necessary and sufficient for tension‐dependent localization to adherens junctions. The LIM domains of TRIP6, LIMD1, and certain other LIM domain proteins have been shown to bind to actin networks under strain/tension. Consistent with this, we show that TRIP6 and LIMD1 colocalize with the ends of actin fibers at adherens junctions. Point mutations in a key conserved residue in each LIM domain that are predicted to impair binding to f‐actin under strain inhibits TRIP6 and LIMD1 localization to adherens junctions and their ability to bind to and recruit LATS1 to adherens junctions. Together these results show that the ability of TRIP6 and LIMD1 to bind to strained actin underlies their ability to localize to adherens junctions and regulate LATS1 in response to mechanical tension.

中文翻译：

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LIMD1 和 TRIP6 LIM 结构域结合应变 f-肌动蛋白的能力对于它们张力依赖性定位到粘附连接以及与 Hippo 通路激酶 LATS1 的关联至关重要

响应机械张力调节 Hippo 通路信号传导的关键步骤是将 LIM 结构域蛋白 TRIP6 和 LIMD1 募集到粘附连接处。机械张力还会触发 TRIP6 和 LIMD1 结合并抑制 Hippo 通路激酶 LATS1。TRIP6 和 LIMD1 如何被招募到粘附连接以响应张力尚不清楚，但之前的研究表明它们可能受到粘附连接处已知的机械感觉蛋白 α-catenin 和 vinculin 的调节。我们发现 TRIP6 和 LIMD1 的三个 LIM 结构域对于粘附连接的张力依赖性定位是必要且充分的。TRIP6、LIMD1 和某些其他 LIM 结构域蛋白的 LIM 结构域已被证明在应变/张力下与肌动蛋白网络结合。与此一致的是，我们发现 TRIP6 和 LIMD1 与粘附连接处的肌动蛋白纤维末端共定位。每个 LIM 结构域中关键保守残基的点突变预计会损害应变下与 f-肌动蛋白的结合，从而抑制 TRIP6 和 LIMD1 定位到粘附连接以及它们结合和招募 LATS1 到粘附连接的能力。这些结果共同表明 TRIP6 和 LIMD1 与应变肌动蛋白结合的能力是它们定位于粘附连接并响应机械张力调节 LATS1 的能力的基础。