Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
Nat Commun. 2021 Mar 25;12(1):1756. doi: 10.1038/s41467-021-22010-9.
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.
核蛋白 lamin A/C 的水平对于核机械转导至关重要。已知 lamin A/C 的水平与间质组织的组织硬度和细胞外基质水平成正比。但是在细胞与细胞外基质之间没有强烈相互作用的上皮组织中，lamin A/C 是如何被调节的尚不清楚。在这里，我们在上皮组织中表明 lamin A/C 的水平与顶端-基底细胞压缩成正比，而与组织硬度无关。利用果蝇上皮组织中的遗传干扰，我们表明顶端-基底细胞压缩通过使核变形来调节 lamin A/C 的水平。此外，在哺乳动物上皮细胞中，我们表明核变形通过调节 lamin A/C 丝氨酸 22 磷酸化水平来调节 lamin A/C 水平，丝氨酸 22 是 lamin A/C 降解的靶标。总之，我们的结果揭示了 lamin A/C 调节的一种机制，这可能为理解上皮组织中的核机械转导提供关键的见解。
