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

K Venkatesan Iyer, Anna Taubenberger, Salma Ahmed Zeidan, Natalie A Dye, Suzanne Eaton, Frank Jülicher

Nature communications 2021 Mar 25

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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.

Citation

K Venkatesan Iyer, Anna Taubenberger, Salma Ahmed Zeidan, Natalie A Dye, Suzanne Eaton, Frank Jülicher. Apico-basal cell compression regulates Lamin A/C levels in epithelial tissues. Nature communications. 2021 Mar 25;12(1):1756