abLIM1 constructs non-erythroid cortical actin networks to prevent mechanical tension-induced blebbing.
abLIM1 constructs non-erythroid cortical actin networks to prevent mechanical tension-induced blebbing.
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abLIM1 构建非红系皮质肌动蛋白网络以防止机械张力引起的起泡
DOI：
10.1038/s41421-018-0040-3
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发表时间：
2018
期刊：
影响因子：
33.5
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Li G;Huang S;Yang S;Wang J;Cao J;Czajkowsky DM;Shao Z;Zhu X
细胞皮层是质膜下的一层细胞骨架网络，由丝状肌动蛋白（F-肌动蛋白）和皮层蛋白（包括血影蛋白、内收蛋白和肌球蛋白）形成。它为细胞提供适当的硬度，弹性和表面张力，以允许形态发生，分裂和迁移。虽然其结构和形成已在红细胞中被广泛研究，但由于结构复杂性和多功能性，它们在非红细胞中知之甚少。在这项研究中，我们确定肌动蛋白结合蛋白abLIM 1作为一种新的非红细胞特异性皮层组织者。内源性abLIM 1与皮质βII血影蛋白共定位，但过表达后重新分布到厚的皮质肌动蛋白束。abLIM 1在体内与主要皮质蛋白如血影蛋白和内收蛋白相关。通过RNAi耗尽abLIM 1在伸展或迁移的RPE 1细胞的膜突起期间诱导突出的起泡，并且损害迁移效率。通过培养细胞至融合或抑制肌球蛋白活性来降低皮质张力，可抑制起泡表型。abLIM 1耗尽的RPE 1或U2 OS细胞缺乏在对照细胞中观察到的密集交织的皮质肌动蛋白网，但是沿着细胞的长轴沿着有丰富的长皮质肌动蛋白束。体外实验表明，abLIM 1能够交联和捆绑F-肌动蛋白，诱导密集的F-肌动蛋白网络的形成。因此，abLIM 1在非红系细胞中控制致密互连的皮质肌动蛋白网络的形成，以防止在细胞活动如扩散和迁移期间机械张力诱导的起泡。
The cell cortex is a layer of cytoskeletal networks underneath the plasma membrane, formed by filamentous actin (F-actin) and cortex proteins including spectrin, adducin, and myosin. It provides cells with proper stiffness, elasticity, and surface tension to allow morphogenesis, division, and migration. Although its architecture and formation have been widely studied in red blood cells, they are poorly understood in non-erythrocytes due to structural complexity and versatile functions. In this study, we identify the actin-binding protein abLIM1 as a novel non-erythroid cell-specific cortex organizer. Endogenous abLIM1 colocalized with cortical βII spectrin but upon overexpression redistributed to thick cortical actin bundles. abLIM1 associated with major cortex proteins such as spectrins and adducin in vivo. Depletion of abLIM1 by RNAi induced prominent blebbing during membrane protrusions of spreading or migrating RPE1 cells and impaired migration efficiency. Reducing cortical tensions by culturing the cells to confluency or inhibiting myosin activity repressed the blebbing phenotype. abLIM1-depleted RPE1 or U2OS cells lacked the dense interwoven cortical actin meshwork observed in control cells but were abundant in long cortical actin bundles along the long axis of the cells. In-vitro assays indicated that abLIM1 was able to crosslink and bundle F-actin to induce dense F-actin network formation. Therefore, abLIM1 governs the formation of dense interconnected cortical actin meshwork in non-erythroid cells to prevent mechanical tension-induced blebbing during cellular activities such as spreading and migration.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
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影响因子：
13.6
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DOI：
10.1073/pnas.1207968109
发表时间：
2012-09-04
影响因子：
11.1
作者：
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Paluch, Ewa
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DOI：
10.1126/science.aab3500
发表时间：
2015-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li D;Shao L;Chen BC;Zhang X;Zhang M;Moses B;Milkie DE;Beach JR;Hammer JA 3rd;Pasham M;Kirchhausen T;Baird MA;Davidson MW;Xu P;Betzig E
通讯作者：
Betzig E