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细胞大小依赖性的 Ezrin 调节通过抵消肌球蛋白 II 介导的收缩来决定上皮细胞对拉伸的弹性。

Cell-size-dependent regulation of Ezrin dictates epithelial resilience to stretch by countering myosin-II-mediated contractility.

机构信息

Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India.

Department of Chemical Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India.

出版信息

Cell Rep. 2024 Jun 25;43(6):114271. doi: 10.1016/j.celrep.2024.114271. Epub 2024 May 31.

Abstract

The epithelial adaptations to mechanical stress are facilitated by molecular and tissue-scale changes that include the strengthening of junctions, cytoskeletal reorganization, and cell-proliferation-mediated changes in tissue rheology. However, the role of cell size in controlling these properties remains underexplored. Our experiments in the zebrafish embryonic epidermis, guided by theoretical estimations, reveal a link between epithelial mechanics and cell size, demonstrating that an increase in cell size compromises the tissue fracture strength and compliance. We show that an increase in E-cadherin levels in the proliferation-deficient epidermis restores epidermal compliance but not the fracture strength, which is largely regulated by Ezrin-an apical membrane-cytoskeleton crosslinker. We show that Ezrin fortifies the epithelium in a cell-size-dependent manner by countering non-muscle myosin-II-mediated contractility. This work uncovers the importance of cell size maintenance in regulating the mechanical properties of the epithelium and fostering protection against future mechanical stresses.

摘要

上皮细胞对机械应激的适应性是通过分子和组织尺度的变化来实现的,包括连接的加强、细胞骨架的重组以及细胞增殖介导的组织流变学变化。然而,细胞大小在控制这些特性中的作用仍未得到充分探索。我们在斑马鱼胚胎表皮中的实验,受到理论估计的指导,揭示了上皮力学和细胞大小之间的联系,表明细胞大小的增加会损害组织的断裂强度和顺应性。我们表明,在增殖缺陷的表皮中增加 E-cadherin 水平可以恢复表皮顺应性,但不能恢复断裂强度,而断裂强度主要受 Ezrin(一种顶端膜-细胞骨架交联物)调节。我们表明,Ezrin 通过对抗非肌肉肌球蛋白-II 介导的收缩性,以细胞大小依赖的方式增强上皮组织。这项工作揭示了维持细胞大小在调节上皮组织力学特性和促进对未来机械应激的保护中的重要性。

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