Nuclear pore complexes concentrate on Actin/LINC/Lamin nuclear lines in response to mechanical stress in a SUN1 dependent manner.
Nuclear pore complexes concentrate on Actin/LINC/Lamin nuclear lines in response to mechanical stress in a SUN1 dependent manner.
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DOI：
10.1016/j.heliyon.2022.e12147
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发表时间：
2022-12
期刊：
影响因子：
4
通讯作者：
Beckerle, Mary C.
中科院分区：
文献类型：
--
作者：
Smith, Mark A.;Blankman, Elizabeth;Jensen, Christopher C.;Hoffman, Laura M.;Ullman, Katharine S.;Beckerle, Mary C.
关键词：
在细胞拉伸过程中，形成的强有力的肌动球蛋白应力纤维（SF）在信息从细胞质向细胞核的传递中起着关键作用。肌动蛋白/LINC/核纤层蛋白（ALL）核系提供肌动蛋白细胞骨架和核纤层蛋白核骨架之间的机械连接。为了理解ALL系的建立，我们使用暴露于周期性拉伸的细胞的活细胞成像。我们发现，核孔复合物（NPC）集中沿着所有的线产生的单轴循环拉伸。ALL相关的NPC显示核孔蛋白Pom 121、TPR和Nup 153相对于远离ALL系的核孔蛋白的荧光强度增加。在这里，我们测试的假设，LINC复杂的组成部分，ALL线，SUN 1参与整合的NPC与ALL线。我们产生了CRISPR SUN 1敲低和敲除细胞系，并表明SUN 1对NPC正常整合到ALL系中至关重要。SUN 1的缺失或消除显著减少了NPC/ALL系整合，证明了SUN 1在将NPC募集或稳定到ALL系核膜的离散亚结构域中的关键作用。这项工作为细胞通过核膜重塑对机械力做出反应的机制提供了新的见解。LINC复合蛋白;核孔复合物;机械力转导;肌动蛋白应力纤维;肌动蛋白/LINC/核纤层细胞系。
Formation of robust actomyosin stress fibers (SF) in response to cell stretch plays a key role in the transfer of information from the cytoplasm into the nucleus. Actin/LINC/Lamin (ALL) nuclear lines provide mechanical linkage between the actin cytoskeleton and the lamin nucleoskeleton across the nuclear envelope. To understand the establishment of ALL lines, we used live cell imaging of cells exposed to cyclic stretch. We discovered that nuclear pore complexes (NPCs) concentrate along ALL lines that are generated in response to uniaxial cyclic stretch. The ALL-associated NPCs display increased fluorescence intensity of nucleoporins Pom121, TPR and Nup153 relative to nucleoporins that are distal to the ALL lines. Here we test the hypothesis that a LINC complex component of ALL lines, SUN1 is involved in the integration of NPCs with ALL lines. We generated CRISPR SUN1 knockdown and knockout cell lines and show that SUN1 is essential for normal integration of NPCs to ALL lines. Loss or elimination of SUN1 significantly diminishes NPC/ALL line integration, demonstrating a key role for SUN1 in the recruitment or stabilization of NPCs to a discrete subdomain of the nuclear envelope at ALL lines. This work provides new insight into the mechanism by which cells respond to mechanical force through nuclear envelope remodeling. LINC complex proteins; Nuclear pore complex; Mechanotransduction; Actin stress fibers; Actin/LINC/Lamin lines.
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影响因子：
4.6
作者：
Jäckel C;Nogueira MS;Ehni N;Kraus C;Ranke J;Dohmann M;Noessner E;Nelson PJ
通讯作者：
Nelson PJ
影响因子：
14.9
作者：
Li P;Noegel AA
通讯作者：
Noegel AA
影响因子：
21.3
作者：
Kirby TJ;Lammerding J
通讯作者：
Lammerding J
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
3.3
作者：
Hoffman LM;Smith MA;Jensen CC;Yoshigi M;Blankman E;Ullman KS;Beckerle MC
通讯作者：
Beckerle MC