Keeping the LINC: the importance of nucleocytoskeletal coupling in intracellular force transmission and cellular function.
Keeping the LINC: the importance of nucleocytoskeletal coupling in intracellular force transmission and cellular function.
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DOI：
10.1042/bst20110686
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发表时间：
2011-12
影响因子：
3.9
通讯作者：
Lammerding J
中科院分区：
文献类型：
--
作者：
Lombardi ML;Lammerding J
在细胞核和细胞骨架之间提供稳定的物理连接对于广泛的细胞功能是必不可少的，并且还可以通过细胞骨架向细胞核传递细胞内和细胞外的机械刺激来参与机械传感。位于核膜上的Nesprins蛋白和SUN蛋白形成LINC（细胞核与细胞骨架连接物）复合物，将细胞核与细胞骨架连接起来；底层核层有助于将LINC复合物组分锚定在核膜上。LINC复合物的破坏或层粘连蛋白的缺失可导致核周肌动蛋白和中间丝网络受到干扰，并导致严重的功能缺陷，包括核定位、细胞极化和细胞运动受损。最近的研究已经确定LINC复合物是核膜上的主要力传递元件，并表明上述许多缺陷可归因于细胞核和细胞骨架之间的力传递受到干扰。因此，与肌营养不良和心肌病相关的nesprins、SUN蛋白或层粘连蛋白的突变可能削弱或完全消除核膜处的LINC复合物功能，导致细胞内力传递受损，从而破坏关键的细胞功能。
Providing a stable physical connection between the nucleus and the cytoskeleton is essential for a wide range of cellular functions and could also participate in mechanosensing by transmitting intra- and extracellular mechanical stimuli via the cytoskeleton to the nucleus. Nesprins and SUN proteins, located at the nuclear envelope, form the LINC (Linker of Nucleus and Cytoskeleton) complex that connects the nucleus to the cytoskeleton; underlying nuclear lamins contribute to anchoring LINC complex components at the nuclear envelope. Disruption of the LINC complex or loss of lamins can result in disturbed perinuclear actin and intermediate filament networks and causes severe functional defects, including impaired nuclear positioning, cell polarization, and cell motility. Recent studies have identified the LINC complex as the major force transmitting element at the nuclear envelope and suggest that many of the aforementioned defects can be attributed to disturbed force transmission between the nucleus and the cytoskeleton. Thus, mutations in nesprins, SUN proteins or lamins, which have been linked to muscular dystrophies and cardiomyopathies, may weaken or completely eliminate LINC complex function at the nuclear envelope and result in impaired intracellular force transmission, thereby disrupting critical cellular functions.