Actomyosin contractility provokes contact inhibition in E-cadherinligated keratinocytes
Actomyosin contractility provokes contact inhibition in E-cadherinligated keratinocytes
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DOI：
10.1038/srep46326
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发表时间：
2017-04-13
影响因子：
4.6
通讯作者：
Sokabe, Masahiro
中科院分区：
文献类型：
--
作者：
Hirata, Hiroaki;Samsonov, Mikhail;Sokabe, Masahiro
融合依赖性的上皮细胞增殖抑制，称为接触抑制，是上皮稳态和器官大小控制的关键。在这里，我们报道在上皮细胞中，角质形成细胞，构成皮肤的分层上皮，具有独特的，不依赖于肌动肌的接触抑制机制。我们观察到，在肌动球蛋白抑制的条件下，细胞间通过e -钙粘蛋白自身接触促进了角质形成细胞的增殖。然而，融合角化细胞中的肌动球蛋白活性抑制β -catenin和YAP的核定位，并导致β -catenin和YAP驱动的细胞增殖减弱。融合性角化细胞形成e -钙粘蛋白介导的点状粘附复合物，其与径向肌动蛋白电缆相连。通过消耗α -连环蛋白来消除肌动蛋白与e -钙粘蛋白的联系，可增加融合角化细胞的增殖。相比之下，强制激活rhoa调节的肌动球蛋白或外用拉力连接e -钙粘蛋白会减弱它们的增殖，这表明e -钙粘蛋白介导的粘附复合物的拉伸应力抑制融合角化细胞的增殖。我们的研究结果强调肌动球蛋白的收缩性是引起角化细胞增殖的汇合依赖性抑制的关键因素。
Confluence-dependent inhibition of epithelial cell proliferation, termed contact inhibition, is crucial for epithelial homeostasis and organ size control. Here we report that among epithelial cells, keratinocytes, which compose the stratified epithelium in the skin, possess a unique, actomyosindependent mechanism for contact inhibition. We have observed that under actomyosin-inhibited conditions, cell-cell contact itself through E-cadherin promotes proliferation of keratinocytes. Actomyosin activity in confluent keratinocytes, however, inhibits nuclear localization of beta-catenin and YAP, and causes attenuation of beta-catenin- and YAP-driven cell proliferation. Confluent keratinocytes develop E-cadherin-mediated punctate adhesion complexes, to which radial actin cables are connected. Eliminating the actin-to-E-cadherin linkage by depleting alpha-catenin increases proliferation of confluent keratinocytes. By contrast, enforced activation of RhoA-regulated actomyosin or external application of pulling force to ligated E-cadherin attenuates their proliferation, suggesting that tensile stress at E-cadherin-mediated adhesion complexes inhibits proliferation of confluent keratinocytes. Our results highlight actomyosin contractility as a crucial factor that provokes confluence-dependent inhibition of keratinocyte proliferation.