The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin
The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin
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DOI：
10.1016/j.celrep.2017.07.032
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发表时间：
2017-08-08
期刊：
影响因子：
8.8
通讯作者：
Ohno, Shigeo
中科院分区：
文献类型：
--
作者：
Furukawa, Kana T.;Yamashita, Kazunari;Ohno, Shigeo
圆柱上皮细胞单层的粘附连接处的圆周肌动蛋白皮带控制细胞间表面张力和细胞形状，以维持组织完整性。是与蛋白质（YAP）及其旁系同源物TAZ是在细胞核和细胞质之间穿梭的增殖激活转录共激活剂。先前的研究表明，应激纤维在肌动蛋白细胞骨架中的重要性对于调节YAP核定位的重要性。但是，圆周肌动蛋白带对YAP定位的作用仍然没有照lin。通过操纵肌动蛋白的张力，我们证明了圆周肌动蛋白皮带张力抑制YAP/TAZ核定位。这种抑制需要Merlin，这是一种与粘附连接相关的F-肌动蛋白结合蛋白。 Merlin与YAP/TAZ物理相互作用，抑制需要Merlin的核输出序列。总之，在观察到cardherin和merlin之间的关联因周向肌动蛋白带中的张力减少了，我们的结果表明，释放的Merlin经历了核细胞质的封闭，并介导了从核中导出YAP/TAZ。
Circumferential actin belts underlying the adherens junctions of columnar epithelial cell monolayers control intercellular surface tension and cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.