Mena regulates nesprin-2 to control actin-nuclear lamina associations, trans-nuclear membrane signalling and gene expression.
Mena regulates nesprin-2 to control actin-nuclear lamina associations, trans-nuclear membrane signalling and gene expression.
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DOI：
10.1038/s41467-023-37021-x
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发表时间：
2023-03-23
影响因子：
16.6
通讯作者：
Byron, Adam
中科院分区：
文献类型：
--
作者：
Chee, Frederic Li Mow;Beernaert, Bruno;Griffith, Billie G. C.;Loftus, Alexander E. P.;Kumar, Yatendra;Wills, Jimi C.;Lee, Martin;Valli, Jessica;Wheeler, Ann P.;Armstrong, J. Douglas;Parsons, Maddy;Leigh, Irene M.;Proby, Charlotte M.;von Kriegsheim, Alex;Bickmore, Wendy A.;Frame, Margaret C.;Byron, Adam
细胞与细胞外基质之间的相互作用由整合素粘附复合物介导，在包括机械信号的感知和转导在内的基本细胞过程中起着关键作用。在这里，我们研究了患者源性皮肤鳞状细胞癌细胞中整合素粘附体的系统水平变化，并确定了肌动蛋白调节蛋白Mena是粘附复杂网络的关键节点。Mena在肌动蛋白结合蛋白的子网络中与LINC复合物组分nesprin2相连，并与之相互作用并在核膜上共定位。此外，Mena增强了nesprin2与肌动蛋白细胞骨架和核层的相互作用。crispr介导的Mena缺失导致核形态改变，减少核膜蛋白emerin的酪氨酸磷酸化，并通过向核外周募集其增强子下调免疫调节基因PTX3的表达。我们发现了Mena在核膜上的一个意想不到的作用，在那里它控制着核结构、染色质重定位和基因表达。我们的发现确定了一种通过核膜直接信号传导调节基因转录的粘附蛋白。细胞通过细胞骨架将机械力传递给细胞核。在这里，作者揭示了肌动蛋白调节因子Mena在核膜的力传递中的作用，在那里它调节核结构、染色质组织和基因表达。
Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutaneous squamous cell carcinoma cells and identify the actin regulatory protein Mena as a key node in the adhesion complex network. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We uncover an unexpected role for Mena at the nuclear membrane, where it controls nuclear architecture, chromatin repositioning and gene expression. Our findings identify an adhesion protein that regulates gene transcription via direct signalling across the nuclear envelope. Cells transmit mechanical force to the nucleus via the cytoskeleton. Here, the authors reveal a role for the actin regulator Mena in force transmission at the nuclear envelope, where it regulates nuclear architecture, chromatin organization and gene expression.
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影响因子：
9.2
作者：
Byron, Adam;Morgan, Mark R.;Humphries, Martin J.
通讯作者：
Humphries, Martin J.
DOI：
10.1073/pnas.1214394109
发表时间：
2012-11-20
影响因子：
11.1
作者：
Di Modugno, Francesca;Iapicca, Pierluigi;Nistico, Paola
通讯作者：
Nistico, Paola
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
7.5
作者：
Barton LJ;Soshnev AA;Geyer PK
通讯作者：
Geyer PK
影响因子：
5.8
作者：
Bodenhofer, Ulrich;Kothmeier, Andreas;Hochreiter, Sepp
通讯作者：
Hochreiter, Sepp