Hippo pathway regulation by cell morphology and stress fibers
Hippo pathway regulation by cell morphology and stress fibers
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DOI：
10.1242/dev.070987
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发表时间：
2011-09-15
期刊：
影响因子：
4.6
通讯作者：
Sasaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Wada, Ken-Ichi;Itoga, Kazuyoshi;Sasaki, Hiroshi
Hippo信号通路在细胞增殖调控中起重要作用。细胞密度调节培养细胞的Hippo通路；然而，细胞检测密度的机制仍不清楚。在这项研究中，我们证明了细胞形态的变化是一个关键因素。对未接触的单细胞进行形态学处理后，细胞呈扁平铺展，细胞核呈圆形致密，细胞质呈Yap。应激纤维随着细胞面积的扩大而增加，f -肌动蛋白调节Yap下游的细胞形态。细胞形态和f -肌动蛋白调节Yap的磷酸化，而f -肌动蛋白的作用被Lats的调节所抑制。我们的研究结果表明，细胞形态是Hippo通路调控的一个重要因素，Hippo通路是由作用于Lats上游或Lats上的由F-actin组成的应力纤维介导的，细胞可以通过其产生的形态来检测密度。这种细胞形态（应力-纤维）介导的机制可能与涉及Hippo通路的细胞-细胞接触（粘附）介导的机制合作，实现细胞增殖的密度依赖性控制。
The Hippo signaling pathway plays an important role in regulation of cell proliferation. Cell density regulates the Hippo pathway in cultured cells; however, the mechanism by which cells detect density remains unclear. In this study, we demonstrated that changes in cell morphology are a key factor. Morphological manipulation of single cells without cell-cell contact resulted in flat spread or round compact cells with nuclear or cytoplasmic Yap, respectively. Stress fibers increased in response to expanded cell areas, and F-actin regulated Yap downstream of cell morphology. Cell morphology-and F-actin-regulated phosphorylation of Yap, and the effects of F-actin were suppressed by modulation of Lats. Our results suggest that cell morphology is an important factor in the regulation of the Hippo pathway, which is mediated by stress fibers consisting of F-actin acting upstream of, or on Lats, and that cells can detect density through their resulting morphology. This cell morphology (stress-fiber)-mediated mechanism probably cooperates with a cell-cell contact (adhesion)-mediated mechanism involving the Hippo pathway to achieve density-dependent control of cell proliferation.