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

AbstractThe 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.

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

10.1101/2020.05.18.102509 ◽

2020 ◽

Author(s):

K Venkatesan Iyer ◽

Natalie A. Dye ◽

Suzanne Eaton ◽

Frank Jülicher

Keyword(s):

Basal Cell ◽

Mdck Cells ◽

Nuclear Lamina ◽

Lamin A ◽

Mechanical Coupling ◽

Nuclear Mechanics ◽

Epithelial Tissues ◽

Nuclear Lamin ◽

Genetic Perturbations ◽

Cell Shapes

ABSTRACTNuclear lamina bridges mechanical forces from the cytoskeleton to the nucleus, to initiate nuclear mechanotransduction. The concentration of nuclear Lamin proteins, particularly Lamin A/C is crucial for the mechanical properties of the nucleus and nuclear mechanotransduction. Recent studies in mesenchymal tissues show that the concentration of Lamin A/C scales with stiffness and concentration of the underlying extracellular matrix (ECM). But in epithelial tissues, that lack a strong cell-ECM interaction, it is still unclear how Lamin A/C is regulated. Here, we show that concentration of Lamin A/C in epithelial tissues scales with apico-basal compression of cells and is independent of ECM concentration. But, ectopically altering the concentration of Lamin A/C does not influence cell shapes in epithelial tissues. Using genetic perturbations in Drosophila epithelial tissues, we reveal that apico-basal cell compression regulates the concentration of Lamin A/C by deforming the nucleus. We observe a similar mechanism of Lamin A/C regulation in mammalian Madin Darby Canine Kidney (MDCK) cells suggesting that this mechanism is evolutionarily conserved. Taken together, our results reveal a unidirectional mechanical coupling between cell mechanics and nuclear mechanics via the regulation of Lamin A/C. We anticipate that mechanism of Lamin A/C regulation that we revealed, could form the basis for understanding nuclear mechanotransduction in epithelial tissues.

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Ultrastructure of Mouse Basal Cell Carcinoma Exhibiting Sebaceous Differentiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600003214 ◽

1980 ◽

Vol 38 ◽

pp. 738-739

Author(s):

Victoria L. Wade ◽

Winslow G. Sheldon ◽

James W. Townsend ◽

William Allaben

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Topical Application ◽

Basal Cell ◽

Sebaceous Gland ◽

Rats And Mice ◽

Mixed Tumors

Sebaceous gland tumors and other tumors exhibiting sebaceous differentiation have been described in humans (1,2,3). Tumors of the sebaceous gland can be induced in rats and mice following topical application of carcinogens (4), but spontaneous mixed tumors of basal cell origin rarely occur in mice.

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