Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus.
Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus.
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孤立的细胞核适应力并揭示了细胞核中的力传导途径。
DOI：
10.1038/ncb2927
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发表时间：
2014-04
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
机械力影响细胞行为的许多方面。通过位于细胞表面、粘附复合物或细胞骨架结构中的受力分子元件来检测力并将其转换为生化信号。细胞核通过细胞骨架以及核骨架和细胞骨架连接体 (LINC) 复合物与细胞表面物理连接，从而允许从粘附到细胞核的快速机械应力传递。尽管已经证明原子核受到力的作用，但力对原子核的直接影响尚不清楚。在这里，我们表明，孤立的原子核能够通过调整其刚度来抵抗所施加的张力，从而对力做出反应。使用磁力镊子，我们发现对 nesprin-1 施加力会引发核硬化，这种硬化不涉及染色质或核肌动蛋白，但需要完整的核纤层和 emerin（一种内核膜蛋白质）。艾默林因受到力的作用而变得酪氨酸磷酸化，并介导对张力的核机械反应。我们的结果表明，机械转导不仅限于细胞表面受体和粘附，还可以发生在细胞核内。
Mechanical forces influence many aspects of cell behavior. Forces are detected and transduced into biochemical signals by force bearing molecular elements located at the cell surface, in adhesion complexes or in cytoskeletal structures. The nucleus is physically connected to the cell surface through the cytoskeleton and the linker of nucleoskeleton and cytoskeleton (LINC) complex, allowing rapid mechanical stress transmission from adhesions to the nucleus. Whereas it has been demonstrated that nuclei experience force, the direct effect of force on the nucleus is not known. Here we show that isolated nuclei are able to respond to force by adjusting their stiffness to resist the applied tension. Using magnetic tweezers, we found that applying force on nesprin-1 triggers nuclear stiffening that does not involve chromatin or nuclear actin, but requires an intact nuclear lamina and emerin, a protein of the inner nuclear membrane. Emerin becomes tyrosine phosphorylated in response to force and mediates the nuclear mechanical response to tension. Our results demonstrate that mechanotransduction is not restricted to cell surface receptors and adhesions but can occur within the nucleus.
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影响因子：
64.5
作者：
Choquet, D;Felsenfeld, DP;Sheetz, MP
通讯作者：
Sheetz, MP
影响因子：
16
作者：
Lim, Ssang-Taek;Chen, Xiao Lei;Llic, Dusko
通讯作者：
Llic, Dusko
影响因子：
4
作者：
Dahl, Kris Noel;Kalinowski, Agnieszka
通讯作者：
Kalinowski, Agnieszka
影响因子：
4
作者：
Provenzano, Paolo P.;Keely, Patricia J.
通讯作者：
Keely, Patricia J.
DOI：
10.1073/pnas.94.3.849
发表时间：
1997-02-04
影响因子：
11.1
作者：
Maniotis, AJ;Chen, CS;Ingber, DE
通讯作者：
Ingber, DE