KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea.
Cells. 2019 Mar 11;8(3):231. doi: 10.3390/cells8030231.
Extracellular mechanical stimuli are translated into biochemical signals inside the cell via mechanotransduction. The nucleus plays a critical role in mechanoregulation, which encompasses mechanosensing and mechanotransduction. The nuclear lamina underlying the inner nuclear membrane not only maintains the structural integrity, but also connects the cytoskeleton to the nuclear envelope. Lamin mutations, therefore, dysregulate the nuclear response, resulting in abnormal mechanoregulations, and ultimately, disease progression. Impaired mechanoregulations even induce malfunction in nuclear positioning, cell migration, mechanosensation, as well as differentiation. To know how to overcome laminopathies, we need to understand the mechanisms of laminopathies in a mechanobiological way. Recently, emerging studies have demonstrated the varying defects from lamin mutation in cellular homeostasis within mechanical surroundings. Therefore, this review summarizes recent findings highlighting the role of lamins, the architecture of nuclear lamina, and their disease relevance in the context of nuclear mechanobiology. We will also provide an overview of the differentiation of cellular mechanics in laminopathy.
细胞外机械刺激通过力学转导转化为细胞内的生化信号。核在力学调节中起着关键作用，包括力学感知和力学转导。内核膜下的核纤层不仅维持结构的完整性，还将细胞骨架连接到核膜。因此，核纤层蛋白的突变会使核反应失调，导致异常的力学调节，最终导致疾病进展。力学调节的受损甚至会导致核定位、细胞迁移、力学感知和分化的功能障碍。要了解如何克服核纤层蛋白病，我们需要从力学生物学的角度理解核纤层蛋白病的机制。最近的研究表明，力学环境中细胞稳态的核纤层蛋白突变会导致不同的缺陷。因此，本综述总结了最近的研究结果，强调了核纤层蛋白、核纤层结构及其在核力学生物学背景下的疾病相关性的作用。我们还将概述细胞力学在核纤层蛋白病中的分化。
