Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes.
Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes.
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DOI：
10.1038/srep33893
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发表时间：
2016-09-21
影响因子：
4.6
通讯作者：
Connelly JT
中科院分区：
文献类型：
--
作者：
Sharili AS;Kenny FN;Vartiainen MK;Connelly JT
肌动蛋白细胞骨架是细胞迁移的经典生物力学介质。虽然已知肌动蛋白也穿梭于细胞核内外，但对其在细胞核内的功能仍知之甚少。在这项研究中，我们研究了核肌动蛋白如何调节角质形成细胞基因表达和细胞行为。通过对正常HaCaT角质形成细胞与过表达野生型β-肌动蛋白或核定位序列标记β-肌动蛋白（NLS-actin）的HaCaT进行基因表达谱分析，发现在核肌动蛋白水平高的角质形成细胞中，MYL9、ITGB1和VCL等多个黏附和细胞骨架基因显著下调。此外，在NLS-actin过表达的细胞中，与转录调控和凋亡相关的基因上调。在功能上，肌动蛋白在细胞核内的积累改变了细胞骨架和局灶黏附组织，抑制了细胞运动。通过敲除输入蛋白9从细胞核中排除内源性肌动蛋白逆转了这种表型并增强了细胞迁移。基于这些发现，我们得出结论，核中肌动蛋白的水平是调节角质形成细胞迁移的转录调节剂。
The actin cytoskeleton is a classic biomechanical mediator of cell migration. While it is known that actin also shuttles in and out of the nucleus, its functions within this compartment remain poorly understood. In this study, we investigated how nuclear actin regulates keratinocyte gene expression and cell behavior. Gene expression profiling of normal HaCaT keratinocytes compared to HaCaTs over-expressing wild-type β-actin or β-actin tagged with a nuclear localization sequence (NLS-actin), identified multiple adhesive and cytoskeletal genes, such as MYL9, ITGB1, and VCL, which were significantly down-regulated in keratinocytes with high levels of nuclear actin. In addition, genes associated with transcriptional regulation and apoptosis were up-regulated in cells over expressing NLS-actin. Functionally, accumulation of actin in the nucleus altered cytoskeletal and focal adhesion organization and inhibited cell motility. Exclusion of endogenous actin from the nucleus by knocking down Importin 9 reversed this phenotype and enhanced cell migration. Based on these findings, we conclude that the level of actin in the nucleus is a transcriptional regulator for tuning keratinocyte migration.
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DOI：
10.1073/pnas.032662899
发表时间：
2002-03-05
影响因子：
11.1
作者：
Rando, OJ;Zhao, KJ;Crabtree, GR
通讯作者：
Crabtree, GR
影响因子：
10.5
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
4.8
作者：
Gineitis, D;Treisman, R
通讯作者：
Treisman, R
影响因子：
64.5
作者：
Horsley, Valerie;Aliprantis, Antonios O.;Fuchs, Elaine
通讯作者：
Fuchs, Elaine