A Zyxin-Mediated Mechanism for Actin Stress Fiber Maintenance and Repair

Smith, Mark A.; Blankman, Elizabeth; Gardel, Margaret L.; Luettjohann, Laura; Waterman‐Storer, Clare M.; Beckerle, Mary C.

doi:10.1016/j.devcel.2010.08.008

Cited by 198 publications

(312 citation statements)

References 51 publications

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“…5A). Zyxin is an actin regulatory protein that localizes to sites of focal adhesions and stress fibers in response to mechanical cues to facilitate actin polymerization and generation of traction force (Beckerle, 1997;Hirata et al, 2008;Smith et al, 2010). In line with this functional role, zyxin upregulation during EMT in NMuMG cells has been reported to be essential for cell migration (Mori et al, 2009), and given that forced expression of Tead2 promotes cancer cell migration or invasion, and metastatic outgrowth of Py2T cells in the lung (Fig.…”

Section: Zyxin Is a Tead2-taz Target Gene Critical For Emtmentioning

confidence: 88%

Tead2 expression levels control Yap/Taz subcellular distribution, zyxin expression, and epithelial-mesenchymal transition

Diepenbruck

Waldmeier

Ivánek

et al. 2014

Journal of Cell Science

115

125

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The cellular changes during an epithelial-mesenchymal transition (EMT) largely rely on global changes in gene expression orchestrated by transcription factors. Tead transcription factors and their transcriptional co-activators Yap and Taz have been previously implicated in promoting an EMT; however, their direct transcriptional target genes and their functional role during EMT have remained elusive. We have uncovered a previously unanticipated role of the transcription factor Tead2 during EMT. During EMT in mammary gland epithelial cells and breast cancer cells, levels of Tead2 increase in the nucleus of cells, thereby directing a predominant nuclear localization of its co-factors Yap and Taz via the formation of Tead2-Yap-Taz complexes. Genome-wide chromatin immunoprecipitation and next generation sequencing in combination with gene expression profiling revealed the transcriptional targets of Tead2 during EMT. Among these, zyxin contributes to the migratory and invasive phenotype evoked by Tead2. The results demonstrate that Tead transcription factors are crucial regulators of the cellular distribution of Yap and Taz, and together they control the expression of genes critical for EMT and metastasis.

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Section: Zyxin Is a Tead2-taz Target Gene Critical For Emtmentioning

confidence: 88%

Tead2 expression levels control Yap/Taz subcellular distribution, zyxin expression, and epithelial-mesenchymal transition

Diepenbruck

Waldmeier

Ivánek

et al. 2014

Journal of Cell Science

115

125

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“…Furthermore, many focal-adhesion-associated proteins are involved in stress fiber regulation. For example, zyxin has been implicated in forcedependent actin polymerization (Hirata et al, 2008), stress fiber mechanosensing (Colombelli et al, 2009) and stress fiber repair (Smith et al, 2010).…”

Section: Different Stress Fiber Types In Animal Cellsmentioning

confidence: 99%

Actin stress fibers – assembly, dynamics and biological roles

Tojkander

Gateva

Lappalainen

2012

Journal of Cell Science

710

720

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SummaryActin filaments assemble into diverse protrusive and contractile structures to provide force for a number of vital cellular processes. Stress fibers are contractile actomyosin bundles found in many cultured non-muscle cells, where they have a central role in cell adhesion and morphogenesis. Focal-adhesion-anchored stress fibers also have an important role in mechanotransduction. In animal tissues, stress fibers are especially abundant in endothelial cells, myofibroblasts and epithelial cells. Importantly, recent live-cell imaging studies have provided new information regarding the mechanisms of stress fiber assembly and how their contractility is regulated in cells. In addition, these studies might elucidate the general mechanisms by which contractile actomyosin arrays, including muscle cell myofibrils and cytokinetic contractile ring, can be generated in cells. In this Commentary, we discuss recent findings concerning the physiological roles of stress fibers and the mechanism by which these structures are generated in cells.

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“…A mechanism that explains stress fiber strain perception by proteins has been suggested for zyxin. Zyxin, which has been implicated in the stabilization of stress fibers (Smith et al, 2010), has several LIM domains, which may act as a ruler to measure the distance between binding sites (Schiller and Fässler, 2013), so that the extent of zyxin binding to a stress fiber would be directly related to the strain in the stress fiber.…”

Section: Stress Fibers: a Critical Link In The Mechanotransduction Chmentioning

confidence: 99%

Model of cellular mechanotransduction via actin stress fibers

Gouget

Hwang

Barakat

2015

Biomech Model Mechanobiol

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Mechanical stresses due to blood flow regulate vascular endothelial cell structure and function and play a key role in arterial physiology and pathology. In particular, the development of atherosclerosis has been shown to correlate with regions of disturbed blood flow where endothelial cells are round and have a randomly organized cytoskeleton. Thus, deciphering the relation between the mechanical environment, cell structure and cell function is a key step towards understanding the early development of atherosclerosis. Recent experiments have demonstrated very rapid (∼100 msec) and long-distance (∼10 µm) cellular mechanotransduction in which prestressed actin stress fibers play a critical role. Here, we develop a model of mechanical signal transmission within a cell by describing strains in a network of prestressed viscoelastic stress fibers following the application of a force to the cell surface. We find force transmission dynamics that are consistent with experimental results. We also show that the extent of stress fiber alignment and the direction of the applied force relative to this alignment are key determinants of the efficiency of mechanical signal transmission. These results are consistent with the link observed experimentally between cytoskeletal organiza- tion, mechanical stress, and cellular responsiveness to stress. Based on these results, we suggest that mechanical strain of actin stress fibers under force constitutes a key link in the mechanotransduction chain.

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A Zyxin-Mediated Mechanism for Actin Stress Fiber Maintenance and Repair

Cited by 198 publications

References 51 publications

Tead2 expression levels control Yap/Taz subcellular distribution, zyxin expression, and epithelial-mesenchymal transition

Tead2 expression levels control Yap/Taz subcellular distribution, zyxin expression, and epithelial-mesenchymal transition

Actin stress fibers – assembly, dynamics and biological roles

Model of cellular mechanotransduction via actin stress fibers

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