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Myosin II contributes to cell-scale actin network treadmilling through network disassembly

机译:Myosin II通过网络拆卸有助于细胞规模的肌动蛋白网络跑步

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摘要

Crawling locomotion of eukaryotic cells is achieved by a process dependent on the actin cytoskeleton: protrusion of the leading edge requires assembly of a network of actin filaments, which must be disassembled at the cell rear for sustained motility. Although ADF/ cofilin proteins have been shown to contribute to actin disassembly3, it is not clear how activity of these locally acting proteins could be coordinated over the distance scale of the whole cell. Here we show that non-muscle myosin II has a direct role in actin network disassembly in crawling cells. In fish keratocytes undergoing motility, myosin II is concentrated in regions at the rear with high rates of network disassembly. Activation of myosin II by ATP in detergent-extracted cytoskeletons results in rear-localized disassembly of the actin network. Inhibition of myosin II activity and stabilization of actin filaments synergistically impede cell motility, suggesting the existence of two disassembly pathways, one of which requires myosin II activity. Our results establish the importance of myosin II as an enzyme for actin network disassembly; we propose that gradual formation and reorganization of an actomyosin network provides an intrinsic destruction timer, enabling long-range coordination of actin network treadmilling in motile cells.
机译:真核细胞的爬行运动是通过依赖于肌动蛋白细胞骨架的过程来实现的:前缘的突出需要组装肌动蛋白丝网络,为了维持持续的运动性,肌动蛋白丝必须在细胞后部分解。尽管已经显示出ADF / cofilin蛋白有助于肌动蛋白的拆卸3,但尚不清楚如何在整个细胞的距离范围内协调这些局部作用蛋白的活性。在这里,我们显示非肌肉肌球蛋白II在爬行细胞的肌动蛋白网络拆卸中具有直接作用。在经历运动的鱼角化细胞中,肌球蛋白II集中在后部区域,网络分解率很高。 ATP在去污剂提取的细胞骨架中被ATP激活的肌球蛋白II导致肌动蛋白网络向后定位。肌球蛋白II活性的抑制和肌动蛋白丝的稳定化协同阻碍细胞运动,表明存在两种拆卸途径,其中一种需要肌球蛋白II活性。我们的结果确立了肌球蛋白II作为肌动蛋白网络拆卸酶的重要性。我们提出,肌动球蛋白网络的逐渐形成和重组提供了一个内在的破坏定时器,从而使运动细胞中肌动蛋白网络跑步的远程协调成为可能。

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  • 来源
    《Nature》 |2010年第7296期|p.373-377|共5页
  • 作者单位

    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA Institute for Creative Technologies, University of Southern California, Marina del Rey, California 90292, USA;

    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA;

    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA Montreal Neurological Institute, Montreal, Quebec, H3A 2B4, Canada;

    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA;

    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA Department of Physics and the Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 32000, Israel;

    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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