Nuclear envelope proteins influence cell cytoarchitecure by poorly understood mechanisms. Here we show that siRNA-mediated silencing of lamin A/C (LMNA) promotes contrasting stress fiber assembly and disassembly in individual cells and within cell populations. We show that LMNA deficient cells have elevated myosin-II bipolar filament accumulations, irregular formation of actin comet tails and podosome-like adhesions, increased steady state nuclear localization of the mechanosensitive transcription factors MKL1 and YAP, and induced expression of some MKL1/Serum Response Factor (SRF) regulated genes such as that encoding myosin-IIA (MYH9). Our studies utilizing live cell imaging and pharmacological inhibition of myosin-II, support a mechanism of deregulated myosin-II self-organizing activity at the nexus of divergent actin cytoskeletal aberrations resultant from LMNA loss. In light of our results, we propose a model of how the nucleus, via linkage to the cytoplasmic actomyosin network, may act to control myosin-II contractile behavior through both mechanical and transcriptional feedback mechanisms.

核被膜蛋白通过了解甚少的机制影响细胞的细胞结构。在这里，我们表明，siRNA介导的层粘连蛋白A / C（LMNA）沉默促进了单个细胞内和细胞群体内相反的应力纤维组装和拆卸。我们显示LMNA缺陷细胞具有升高的肌球蛋白II双极丝积累，肌动蛋白彗星尾巴和足小体样粘连的不规则形成，机械敏感转录因子MKL1和YAP的稳态核定位增加以及某些MKL1 /血清反应的诱导表达因子（SRF）调控的基因，例如编码肌球蛋白IIA（MYH9）的基因。我们利用活细胞成像和肌球蛋白II的药理抑制作用进行研究，支持一种因LMNA丢失导致肌动蛋白II的自组织活性失控的机制。根据我们的结果，我们提出了一个模型，该模型说明了细胞核如何通过与胞质放线菌素网络的连接，通过机械和转录反馈机制来控制肌球蛋白II的收缩行为。