Cellular mechanosensing: getting to the nucleus of it all.
Cellular mechanosensing: getting to the nucleus of it all.
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DOI：
10.1016/j.pbiomolbio.2014.06.009
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发表时间：
2014-08
影响因子：
3.8
通讯作者：
Lammerding J
中科院分区：
文献类型：
--
作者：
Fedorchak GR;Kaminski A;Lammerding J
细胞通过激活特定的基因和信号通路来响应机械力，使细胞适应其物理环境。例子包括响应于运动的肌肉生长，基于其机械负荷的骨重塑，或在流体剪切应力下排列的内皮细胞。虽然所涉及的下游信号传导途径和机械响应基因通常是很好的特点，许多的分子机制的启动“mechanosensing”仍然难以捉摸。在这篇综述中，我们讨论了最近的研究结果和积累的证据表明，细胞核在细胞机械力转导中起着至关重要的作用，包括处理传入的机械力响应信号，甚至直接响应机械力。因此，所涉及的蛋白质的突变或核膜组成的变化可以直接影响机械转导信号，并有助于各种人类疾病的发展和进展，包括肌营养不良症，癌症，以及本次审查的重点，扩张型心肌病。提高洞察力的分子机制核mechanodonduction，部分带来了新技术的出现，研究细胞内力学在高空间和时间分辨率，不仅会导致更好地了解细胞mechanosensing在正常细胞，但也可能导致开发新的治疗方法在许多疾病与核包膜蛋白的缺陷。
Cells respond to mechanical forces by activating specific genes and signaling pathways that allow the cells to adapt to their physical environment. Examples include muscle growth in response to exercise, bone remodeling based on their mechanical load, or endothelial cells aligning under fluid shear stress. While the involved downstream signaling pathways and mechanoresponsive genes are generally well characterized, many of the molecular mechanisms of the initiating ‘mechanosensing’ remain still elusive. In this review, we discuss recent findings and accumulating evidence suggesting that the cell nucleus plays a crucial role in cellular mechanotransduction, including processing incoming mechanoresponsive signals and even directly responding to mechanical forces. Consequently, mutations in the involved proteins or changes in nuclear envelope composition can directly impact mechanotransduction signaling and contribute to the development and progression of a variety of human diseases, including muscular dystrophy, cancer, and the focus of this review, dilated cardiomyopathy. Improved insights into the molecular mechanisms underlying nuclear mechanotransduction, brought in part by the emergence of new technologies to study intracellular mechanics at high spatial and temporal resolution, will not only result in a better understanding of cellular mechanosensing in normal cells but may also lead to the development of novel therapies in the many diseases linked to defects in nuclear envelope proteins.
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影响因子：
56.9
作者：
Baarlink, Christian;Wang, Haicui;Grosse, Robert
通讯作者：
Grosse, Robert
影响因子：
4
作者：
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作者：
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Konstantopoulos, Konstantinos
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作者：
Arimura, T;Helbling-Leclerc, A;Bonne, G
通讯作者：
Bonne, G
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20.1
作者：
Chandar, Suchitra;Yeo, Li Sze;Fatkin, Diane
通讯作者：
Fatkin, Diane