Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila
Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila
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DOI：
10.1242/dev.063545
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发表时间：
2011-06-01
期刊：
影响因子：
4.6
通讯作者：
Janody, Florence
中科院分区：
文献类型：
--
作者：
Fernandez, Beatriz Garcia;Gaspar, Pedro;Janody, Florence
保守的Hippo肿瘤抑制通路是一个关键的激酶级联，通过调节转录共激活子Yorkie的核输入和活性来控制组织生长。在这里，我们报道了调节肌动蛋白聚合的肌动蛋白封盖蛋白α β异二聚体也通过抑制Yorkie活性来抑制不适当的组织生长。Capping蛋白活性的丧失导致顶端F-actin的异常积累，Hippo通路活性降低，以及一些促进细胞存活和增殖的Yorkie靶基因的异位表达。另外两种肌动蛋白调节蛋白Cofilin和环化酶相关蛋白Capulet的减少会导致f -肌动蛋白的异常积累，但只有Capulet的缺失才会像Capping蛋白一样引起异位Yorkie活性。有趣的是，当Hippo通路活性降低或消除时，f -肌动蛋白也会异常积累，而不依赖于Yorkie活性，而Hippo通路成分的过度表达可以部分逆转Capping蛋白缺失细胞中f -肌动蛋白的异常积累。综上所述，这些发现表明Hippo通路活性和肌动蛋白丝动力学之间存在一种新的相互作用，这对正常生长控制至关重要。
The conserved Hippo tumor suppressor pathway is a key kinase cascade that controls tissue growth by regulating the nuclear import and activity of the transcription co-activator Yorkie. Here, we report that the actin-Capping Protein alpha beta heterodimer, which regulates actin polymerization, also functions to suppress inappropriate tissue growth by inhibiting Yorkie activity. Loss of Capping Protein activity results in abnormal accumulation of apical F-actin, reduced Hippo pathway activity and the ectopic expression of several Yorkie target genes that promote cell survival and proliferation. Reduction of two other actin-regulatory proteins, Cofilin and the cyclase-associated protein Capulet, cause abnormal F-actin accumulation, but only the loss of Capulet, like that of Capping Protein, induces ectopic Yorkie activity. Interestingly, F-actin also accumulates abnormally when Hippo pathway activity is reduced or abolished, independently of Yorkie activity, whereas overexpression of the Hippo pathway component expanded can partially reverse the abnormal accumulation of F-actin in cells depleted for Capping Protein. Taken together, these findings indicate a novel interplay between Hippo pathway activity and actin filament dynamics that is essential for normal growth control.