Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension.
Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension.
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DOI：
10.1038/nmat4389
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发表时间：
2015-12
期刊：
影响因子：
41.2
通讯作者：
Vogel V
中科院分区：
文献类型：
--
作者：
Ihalainen TO;Aires L;Herzog FA;Schwartlander R;Moeller J;Vogel V
核层蛋白在细胞质信号传导和核事件之间的交叉中起着核心作用。在这里，我们发现在已知上调细胞收缩性的环境条件下，至少两个N端和c端层蛋白表位在核膜的基底侧是不可接近的。在发生成骨（但不发生脂肪形成）的人间充质干细胞中，以及在粘附刚性（但不软）聚丙烯酰胺水凝胶的成纤维细胞中，a型层粘连蛋白的igg结构域的构象表位更多地埋在基底核包膜中，而不是顶端核包膜。这种层的结构极化是由压缩力促进的，在细胞扩散过程中出现，需要层蛋白A/C多聚，完整的核骨架-细胞骨架键（LINC），以及顶端-肌动蛋白应力-纤维组装。值得注意的是，所鉴定的Igepitope与emerin， DNA和组蛋白结合位点重叠，并且包含各种板状病突变位点。我们的发现应该有助于破译细胞微环境的物理特性如何调节核事件。
Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Igepitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help deciphering how the physical properties of cellular microenvironments regulate nuclear events.