Abstract
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.
Highlights
The levels of nuclear protein Lamin A/C are crucial for nuclear mechanotransduction
We dissected Salivary gland[24], trachea[25], and wing disc[26] epithelial tissues from late third instar Drosophila larvae (Fig. 1a) and immunostained them using an antibody against Lamin C (LamC), the only isoform of Lamin A/C expressed in Drosophila
We show that Lamin A/C levels in epithelial tissues depend on apico-basal cell compression
Summary
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. 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 apicobasal cell compression regulates the levels of Lamin A/C by deforming the nucleus. In the absence of strong interactions with the ECM, it is still unclear how Lamin A/C levels are regulated in these tissues Studying this would be key to understand the role of Lamin A/C in mechanotransduction and the interplay between tissue mechanics and nuclear mechanotransduction in epithelial tissues. In this work, using Drosophila epithelial tissues and mammalian Madin Darby Canine Kidney (MDCK) cells as model systems, we provide strong evidence that apico-basal cell compression is an ECM-independent mechanism for regulation of Lamin A/C in epithelial tissues. By combining genetic perturbations in vivo, and altered cell packing, in cultured mammalian cells, we show that apicobasal cell compression-based regulation of Lamin A/C is evolutionarily conserved in epithelial tissues
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