Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Biochem Biophys Res Commun. 2012 Jul 20;424(1):94-9. doi: 10.1016/j.bbrc.2012.06.073. Epub 2012 Jun 21.
The linker of nucleus and cytoskeleton (LINC) complex, including nesprin-1, has been suggested to be crucial for many biological processes. Previous studies have shown that mutations in nesprin-1 cause abnormal cellular functions and diseases, possibly because of insufficient force transmission to the nucleus through actin filaments (F-actin) bound to nesprin-1. However, little is known regarding the mechanical interaction between the nucleus and F-actin through nesprin-1. In this study, we examined nuclear deformation behavior in nesprin-1 knocked-down endothelial cells (ECs) subjected to uniaxial stretching by evaluating nuclear strain from lateral cross-sectional images. The widths of nuclei in nesprin-1 knocked-down ECs were smaller than those in wild-type cells. In addition, nuclear strain in nesprin-1 knocked-down cells, which is considered to be compressed by the actin cortical layer, increased compared with that in wild-type cells under stretching condition. These results indicate that nesprin-1 knockdown releases the nucleus from the tension of F-actin bound to the nucleus, thereby increasing allowance for deformation before stretching, and that F-actin bound to the nucleus through nesprin-1 causes sustainable force transmission to the nucleus.
核-质连接体（LINC）复合物的连接蛋白，包括核膜孔蛋白 nesprin-1，被认为对许多生物学过程至关重要。先前的研究表明，nesprin-1 的突变会导致细胞功能异常和疾病，这可能是因为与 nesprin-1 结合的肌动蛋白丝（F-actin）向核传递的力不足。然而，关于通过 nesprin-1 实现核与 F-actin 之间的力学相互作用的了解甚少。在这项研究中，我们通过评估侧向横截面图像中的核应变，研究了 nesprin-1 敲低的内皮细胞（EC）在单轴拉伸下的核变形行为。nesprin-1 敲低的 EC 中的核宽度小于野生型细胞中的核宽度。此外，在拉伸条件下，nesprin-1 敲低细胞中的核应变（被认为是由肌动蛋白皮质层压缩的）与野生型细胞相比有所增加。这些结果表明，nesprin-1 敲低会使核从与核结合的 F-actin 的张力中释放出来，从而在拉伸前增加变形的余量，并且通过 nesprin-1 与核结合的 F-actin 会导致持续的力向核传递。
