Mechanical stress triggers nuclear remodeling and the formation of transmembrane actin nuclear lines with associated nuclear pore complexes.
Mechanical stress triggers nuclear remodeling and the formation of transmembrane actin nuclear lines with associated nuclear pore complexes.
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DOI：
10.1091/mbc.e19-01-0027
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发表时间：
2020-07-21
影响因子：
3.3
通讯作者：
Beckerle MC
中科院分区：
文献类型：
--
作者：
Hoffman LM;Smith MA;Jensen CC;Yoshigi M;Blankman E;Ullman KS;Beckerle MC
成纤维细胞的机械刺激诱导肌动蛋白细胞骨架的变化，包括应力纤维（SF）的加强和重新排列。在这里，我们描述了核反应的机械刺激（单轴循环拉伸）。使用荧光显微镜和定量图像分析，我们发现，拉伸诱导的核延伸和对齐垂直的拉伸矢量是依赖于formin调节肌动蛋白聚合。机械敏感性转录因子Yes相关蛋白/PDZ结构域转录辅激活因子（雅普/TAZ）和心肌蛋白相关转录因子（MRTF-A，也称为MKL 1和MAL 1）在细胞核中积累并激活其靶基因以响应单轴循环拉伸。我们表明，跨膜肌动蛋白核（TAN）线诱导的拉伸刺激和核膜（NE）蛋白，包括nesprins，SUN 2，和lamins形式的核骨架和细胞骨架（LINC）复合物的接头对齐肌动蛋白SF。这些NE结构通过改变肌动蛋白的药物治疗（细胞松弛素D和Jasplakinase）或遗传破坏（zyxin基因缺失）而改变，并且它们的持续性需要维持牵张刺激。核孔复合物（NPC）积累在TAN线提供了一个潜在的机制，连接机械提示NPC功能。
Mechanical stimulation of fibroblasts induces changes in the actin cytoskeleton including stress fiber (SF) reinforcement and realignment. Here we characterize the nuclear response to mechanical stimulation (uniaxial cyclic stretch). Using fluorescence microscopy and quantitative image analysis we find that stretch-induced nuclear elongation and alignment perpendicular to the stretch vector are dependent on formin-regulated actin polymerization. The mechanosensitive transcription factors Yes-associated protein/Transcriptional coactivator with PDZ domain (YAP/TAZ) and myocardin-related transcription factor (MRTF-A, also known as MKL1 and MAL1) accumulate in the nucleus and activate their target genes in response to uniaxial cyclic stretch. We show that transmembrane actin nuclear (TAN) lines are induced by stretch stimulation and nuclear envelope (NE) proteins including nesprins, SUN2, and lamins form Linkers of the Nucleoskeleton and Cytoskeleton (LINC) complexes aligned with actin SFs. These NE structures are altered by pharmacological treatments (Cytochalasin D and Jasplakinolide) or genetic disruption (zyxin gene deletion) that alter actin, and their persistence requires maintenance of stretch stimulation. Nuclear pore complexes (NPCs) accumulate at TAN lines providing a potential mechanism for linking mechanical cues to NPC function.