Cytoskeletal tension inhibits Hippo signaling through an Ajuba-Warts complex.

Cytoskeletal tension inhibits Hippo signaling through an Ajuba-Warts complex.
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DOI:
10.1016/j.cell.2014.05.035
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发表时间:
2014-07-03
期刊:
影响因子:
64.5
通讯作者:
Irvine KD
Irvine KD
中科院分区:
生物学1区
文献类型:
--
作者:
Rauskolb C;Sun S;Sun G;Pan Y;Irvine KD

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机械力已经被提出用来调节器官的生长,但缺乏将它们与体内生长调节联系起来的分子机制。我们报道,细胞骨架内张力的增加会促进果蝇的翅膀生长,而细胞骨架张力的降低则会降低翅膀的生长。这些生长上的变化可以用约克的活性变化来解释,约克是一种受河马途径调节的转录因子。肌球蛋白活性对约克的影响在遗传上取决于Ajuba Lim蛋白Jub,它是河马途径中疣的负调节因子。我们进一步证明了JUB与α-连环蛋白结合,并且细胞骨架张力促进了JUB与黏附连接的结合以及与α-连环蛋白的结合。Jub以一种依赖于紧张的方式将疣招募到接合处。我们的观察描绘了一种机制,将细胞骨架张力与河马途径活动的调节联系起来,提供了对机械力如何调节器官生长的分子理解。
Mechanical forces have been proposed to modulate organ growth, but a molecular mechanism that links them to growth regulation in vivo has been lacking. We report that increasing tension within the cytoskeleton increases Drosophila wing growth, whereas decreasing cytoskeletal tension decreases wing growth. These changes in growth can be accounted for by changes in the activity of Yorkie, a transcription factor regulated by the Hippo pathway. The influence of myosin activity on Yorkie depends genetically on the Ajuba LIM protein Jub, a negative regulator of Warts within the Hippo pathway. We further show that Jub associates with α-catenin, and that its localization to adherens junctions and association with α-catenin are promoted by cytoskeletal tension. Jub recruits Warts to junctions in a tension-dependent manner. Our observations delineate a mechanism that links cytoskeletal tension to regulation of Hippo pathway activity, providing a molecular understanding of how mechanical forces can modulate organ growth.
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