Apico-basal cell compression regulates Lamin A/C levels in epithelial tissues

The levels of nuclear protein Lamin A/C are crucial for nuclear mechanotransduction. Lamin A/C levels are known to scale with tissue stiffness and extracellular matrix levels in mesenchymal tissues. But in epithelial tissues, where cells lack a strong interaction with the extracellular matrix, it is unclear how Lamin A/C is regulated. Here, we show in epithelial tissues that Lamin A/C levels scale with apico-basal cell compression, independent of tissue stiffness. Using genetic perturbations in Drosophila epithelial tissues, we show that apico-basal cell compression regulates the levels of Lamin A/C by deforming the nucleus. Further, in mammalian epithelial cells, we show that nuclear deformation regulates Lamin A/C levels by modulating the levels of phosphorylation of Lamin A/C at Serine 22, a target for Lamin A/C degradation. Taken together, our results reveal a mechanism of Lamin A/C regulation which could provide key insights for understanding nuclear mechanotransduction in epithelial tissues. The nuclear lamina bridges mechanical forces from the cytoskeleton to the nucleus, and while Lamin A/C is known to be crucial for this process, its regulation remains unclear. Here the authors show that levels of Lamin A/C scale with apico-basal compression of cells independently of tissue stiffness using Drosophila epithelial tissues and mammalian cells.

Automated summary

The study found that in epithelial tissues, the levels of Lamin A/C change with apico-basal cell compression independently of tissue stiffness. Nuclear deformation and phosphorylation levels of Lamin A/C are key factors in regulating Lamin A/C levels.