Vimentin intermediate filaments and filamentous actin form unexpected interpenetrating networks that redefine the cell cortex.
Vimentin intermediate filaments and filamentous actin form unexpected interpenetrating networks that redefine the cell cortex.
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DOI：
10.1073/pnas.2115217119
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发表时间：
2022-03-08
影响因子：
11.1
通讯作者：
Weitz DA
中科院分区：
文献类型：
--
作者：
Wu H;Shen Y;Sivagurunathan S;Weber MS;Adam SA;Shin JH;Fredberg JJ;Medalia O;Goldman R;Weitz DA
微丝骨架肌动蛋白（F-肌动蛋白）和波形蛋白中间丝（VIF）是两种主要的细胞骨架成分;它们通常被认为是空间上划分的，并具有明显不同和独立的功能。在这里，我们结合联合收割机两种成像方法，高分辨率结构照明显微镜和冷冻电子断层扫描，以及功能表征，出乎意料地显示，VIFs和F-肌动蛋白在细胞皮质内具有广泛的结构相互作用，并形成互穿网络。这些相互作用对细胞具有非常重要的功能性后果，鉴于F-肌动蛋白的广泛过程，这些结果具有广泛的意义。这些结果深刻地改变了我们对细胞骨架成分贡献的理解，并反驳了VIF和F-肌动蛋白在结构和功能上都是独立的这一普遍观点。真核细胞的细胞骨架主要由丝状蛋白、F-肌动蛋白、微管和中间丝组成的网络组成。细胞骨架组分之间的相互作用在决定细胞结构和调节细胞功能方面是重要的。例如，F-肌动蛋白和微管共同控制细胞的形状和极性，而波形蛋白中间丝（VIF）网络的亚细胞组织和运输取决于它们与微管的相互作用。然而，一般认为，F-肌动蛋白和VIF形成两个共存但独立的网络，由于观察到的空间分布和功能的差异，它们是独立的。在本文中，我们提出了一个更密切的调查F-肌动蛋白和VIF细胞骨架网络之间的结构和功能的相互作用。我们使用结构化照明显微镜和冷冻电子断层扫描的VIF和F-肌动蛋白网络的细胞皮质内的结构特征。我们发现，VIFs和F-actin形成了一个互穿网络（IPN），在多个长度尺度上相互作用，VIFs是F-actin应力纤维的组成部分。从测量的恢复细胞收缩性短暂拉伸后，我们发现，IPN结构的结果在增强收缩力，有助于细胞的弹性。对细胞中重构网络和动态测量的研究表明VIF和F-肌动蛋白之间存在直接和特定的关联。从这些结果中，我们得出结论，VIFs和F-肌动蛋白协同工作，无论是在它们的结构和功能。这些结果深刻地改变了我们对细胞骨架组成部分的理解，特别是中间丝和F-肌动蛋白之间的相互作用。
Filamentous actin (F-actin) and vimentin intermediate filaments (VIFs) are two major cytoskeletal components; they are generally thought to be spatially compartmentalized and to have distinctly different and independent functions. Here we combine two imaging methods, high-resolution structured illumination microscopy and cryo-electron tomography, as well as functional characterizations, to show that unexpectedly, VIFs and F-actin have extensive structural interactions within the cell cortex and form interpenetrating networks. These interactions have very important functional consequences for cells, which are broadly significant given the wide range of processes attributed to F-actin. These results profoundly alter our understanding of the contributions of cytoskeletal components and counter the common belief that VIFs and F-actin are independent in both structure and function. The cytoskeleton of eukaryotic cells is primarily composed of networks of filamentous proteins, F-actin, microtubules, and intermediate filaments. Interactions among the cytoskeletal components are important in determining cell structure and in regulating cell functions. For example, F-actin and microtubules work together to control cell shape and polarity, while the subcellular organization and transport of vimentin intermediate filament (VIF) networks depend on their interactions with microtubules. However, it is generally thought that F-actin and VIFs form two coexisting but separate networks that are independent due to observed differences in their spatial distribution and functions. In this paper, we present a closer investigation of both the structural and functional interplay between the F-actin and VIF cytoskeletal networks. We characterize the structure of VIFs and F-actin networks within the cell cortex using structured illumination microscopy and cryo-electron tomography. We find that VIFs and F-actin form an interpenetrating network (IPN) with interactions at multiple length scales, and VIFs are integral components of F-actin stress fibers. From measurements of recovery of cell contractility after transient stretching, we find that the IPN structure results in enhanced contractile forces and contributes to cell resilience. Studies of reconstituted networks and dynamic measurements in cells suggest direct and specific associations between VIFs and F-actin. From these results, we conclude that VIFs and F-actin work synergistically, both in their structure and in their function. These results profoundly alter our understanding of the contributions of the components of the cytoskeleton, particularly the interactions between intermediate filaments and F-actin.
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影响因子：
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64.5
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1083/jcb.201607045
发表时间：
2017-06-05
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
Etienne-Manneville S