Nuclear mechanics and mechanotransduction in health and disease.
Nuclear mechanics and mechanotransduction in health and disease.
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DOI：
10.1016/j.cub.2013.11.009
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发表时间：
2013-12-16
期刊：
影响因子：
9.2
通讯作者：
Lammerding, Jan
中科院分区：
文献类型：
--
作者：
Isermann, Philipp;Lammerding, Jan
细胞核是真核细胞的决定性特征，通常代表最大的细胞器。在过去的十年中，很明显，细胞核通过所谓的LINC（核骨架和细胞骨架的连接物）复合物紧密地整合到细胞的结构网络中，这使得细胞核和细胞骨架之间的力能够传递。细胞核和细胞骨架之间的这种物理连接对于广泛的细胞功能是必不可少的，包括细胞核内的运动和定位、细胞骨架组织、细胞极化和细胞迁移。最近的报道进一步表明，通过细胞骨架从细胞外基质传递到细胞核的力也可能通过触发力诱导的核结构变化直接促进细胞探测其机械环境的能力。此外，细胞核的物理特性在细胞在三维（3-D）环境中的迁移过程中起着至关重要的作用，在三维（3-D）环境中，细胞通常必须穿过小于核直径的狭窄区域，例如在发育、伤口愈合或癌症转移过程中。在这篇综述中，我们简要概述了LINC复合物蛋白和层粘连蛋白如何促进核-细胞骨架偶联，重点介绍了最近关于细胞核在三维环境中细胞机械转导和细胞运动中的作用的发现，并讨论了这些核包膜蛋白表达的突变和/或变化如何导致广泛的人类疾病，包括肌肉萎缩症、扩张型心肌病和早衰。
The nucleus is the defining feature of eukaryotic cells and often represents the largest organelle. Over the past decade, it has become apparent that the nucleus is tightly integrated into the structural network of the cell through so-called LINC (Linker of the nucleoskeleton and cytoskeleton) complexes, which enable transmission of forces between the nucleus and cytoskeleton. This physical connection between the nucleus and the cytoskeleton is essential for a broad range of cellular functions, including intracellular nuclear movement and positioning, cytoskeletal organization, cell polarization, and cell migration. Recent reports further indicate that forces transmitted from the extracellular matrix to the nucleus via they cytoskeleton may also directly contribute to the cell's ability to probe its mechanical environment by triggering force-induced changes in nuclear structures. In addition, it is now emerging that the physical properties of the nucleus play a crucial role during cell migration in three-dimensional (3-D) environments, where cells often have to transit through narrow constrictions smaller than the nuclear diameter, e.g., during development, wound healing, or cancer metastasis. In this review, we provide a brief overview of how LINC complex proteins and lamins facilitate nucleo-cytoskeletal coupling, highlight recent findings regarding the role of the nucleus in cellular mechanotransduction and cell motility in 3-D environments, and discuss how mutations and/or changes in the expression of these nuclear envelope proteins can result in a broad range of human diseases, including muscular dystrophy, dilated cardiomyopathy, and premature aging.
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