Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Strasse 38, Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden, Germany.
Curr Biol. 2019 Feb 18;29(4):578-591.e5. doi: 10.1016/j.cub.2019.01.021. Epub 2019 Feb 7.
Studying how epithelia respond to mechanical stresses is key to understanding tissue shape changes during morphogenesis. Here, we study the viscoelastic properties of the Drosophila wing epithelium during pupal morphogenesis by quantifying mechanical stress and cell shape as a function of time. We find a delay of 8 h between maximal tissue stress and maximal cell elongation, indicating a viscoelastic deformation of the tissue. We show that this viscoelastic behavior emerges from the mechanosensitivity of endocytic E-cadherin turnover. The increase in E-cadherin turnover in response to stress is mediated by mechanosensitive relocalization of the E-cadherin binding protein p120-catenin (p120) from cell junctions to cytoplasm. Mechanosensitivity of E-cadherin turnover is lost in p120 mutant wings, where E-cadherin turnover is constitutively high. In this mutant, the relationship between mechanical stress and stress-dependent cell dynamics is altered. Cells in p120 mutant deform and undergo cell rearrangements oriented along the stress axis more rapidly in response to mechanical stress. These changes imply a lower viscosity of wing epithelium. Taken together, our findings reveal that p120-dependent mechanosensitive E-cadherin turnover regulates viscoelastic behavior of epithelial tissues.
研究上皮细胞如何响应机械应力对于理解形态发生过程中组织形状的变化至关重要。在这里，我们通过定量测量机械应力和细胞形状随时间的变化，研究了果蝇翅膀上皮组织在蛹形态发生过程中的粘弹性特性。我们发现，在组织最大应力和最大细胞伸长之间存在 8 小时的延迟，这表明组织存在粘弹性变形。我们表明，这种粘弹性行为源于内吞型 E-钙黏蛋白周转的机械敏感性。E-钙黏蛋白周转对压力的增加是通过机械敏感的 E-钙黏蛋白结合蛋白 p120-连环蛋白（p120）从细胞连接处到细胞质的重新定位来介导的。在 p120 突变翅膀中，E-钙黏蛋白周转的机械敏感性丧失，其中 E-钙黏蛋白周转持续升高。在这种突变体中，机械应力与依赖于应力的细胞动力学之间的关系发生了改变。与机械应力相比，p120 突变体中的细胞更快地变形，并沿应力轴发生细胞重排。这些变化意味着翅膀上皮组织的粘性较低。总之，我们的发现表明，p120 依赖性机械敏感的 E-钙黏蛋白周转调节上皮组织的粘弹性行为。
