Actomyosin-generated tension controls the molecular kinetics of focal adhesions

Wolfenson, Haguy; Bershadsky, Alexander D.; Henis, Yoav I.; Geiger, Benjamin

doi:10.1242/jcs.077388

Cited by 179 publications

(206 citation statements)

References 51 publications

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“…4F). On a 2D surface, t 1/2 values for vinculin were longer than those for paxillin, which accords with other recent investigations (Wolfenson et al, 2011). Comparisons of data collected on 1D and 2D substrates revealed a twofold increase in vinculin t 1/2 rates, which were analogous to the paxillin t 1/2 rates analyzed by FRAP (Fig.…”

Section: Adhesion Longevity Depends On the Cellular Microenvironmentsupporting

confidence: 91%

Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics

Doyle

Kutys

Conti

et al. 2012

Journal of Cell Science

111

112

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SummaryRecent evidence suggests that organization of the extracellular matrix (ECM) into aligned fibrils or fibril-like ECM topographies promotes rapid migration in fibroblasts. However, the mechanisms of cell migration that are altered by these changes in microenvironmental topography remain unknown. Here, using 1D fibrillar migration as a model system for oriented fibrillar 3D matrices, we find that fibroblast leading-edge dynamics are enhanced by 1D fibrillar micropatterns and demonstrate a dependence on the spatial positioning of cell adhesions. Although 1D, 2D and 3D matrix adhesions have similar assembly kinetics, both 1D and 3D adhesions are stabilized for prolonged periods, whereas both paxillin and vinculin show slower turnover rates in 1D adhesions. Moreover, actin in 1D adhesions undergoes slower retrograde flow than the actin that is present in 2D lamellipodia. These data suggest an increase in mechanical coupling between adhesions and protrusive machinery. Experimental reduction of contractility resulted in the loss of 1D adhesion structure and stability, with scattered small and unstable adhesions, and an uncoupling of adhesion protein-integrin stability. Genetic ablation of myosin IIA (MIIA) or myosin IIB (MIIB) isoforms revealed that MIIA is required for efficient migration in restricted environments as well as adhesion maturation, whereas MIIB helps to stabilize adhesions beneath the cell body. These data suggest that restricted cell environments, such as 1D patterns, require cellular contraction through MIIA to enhance adhesion stability and coupling to integrins behind the leading edge. This increase in mechanical coupling allows for greater leading-edge protrusion and rapid cell migration.

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Section: Adhesion Longevity Depends On the Cellular Microenvironmentsupporting

confidence: 91%

Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics

Doyle

Kutys

Conti

et al. 2012

Journal of Cell Science

111

112

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“…Taken together, these data suggest that in wild-type cells β-PIX promotes disassembly of FA via an ability to induce actomyosin relaxation, whereas its loss results in enhanced myosin-mediated actin cytoskeleton contraction leading to an inhibition in FA disassembly. This conclusion is supported by work from others who have shown that the actin cytoskeleton regulates FA disassembly through the regulation of actomyosin tension (Wolfenson et al, 2011).…”

Section: Discussionsupporting

confidence: 59%

Loss of β-PIX inhibits focal adhesion disassembly and promotes keratinocyte motility via myosin light chain activation

Hiroyasu

Stimac

Hopkinson

et al. 2017

Journal of Cell Science

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During healing of the skin, the cytoskeleton of keratinocytes and their matrix adhesions, including focal adhesions (FAs), undergo reorganization. These changes are coordinated by small GTPases and their regulators, including the guanine nucleotide exchange factor β-PIX (also known as ARHGEF7). In fibroblasts, β-PIX activates small GTPases, thereby enhancing migration. In keratinocytes in vitro, β-PIX localizes to FAs. To study β-PIX functions, we generated β-PIX knockdown keratinocytes. During wound closure of β-PIX knockdown cell monolayers, disassembly of FAs is impaired, and their number and size are increased. In addition, in the β-PIX knockdown cells, phosphorylated myosin light chain (MLC; also known as MYL2) is present not only in the leading edge of cells at the wound front, but also in the cells following the front, while p21-activated kinase 2 (PAK2), a regulator of MLC kinase (MYLK), is mislocalized. Inhibition or depletion of MYLK restores FA distribution in β-PIX knockdown cells. Traction forces generated by β-PIX knockdown cells are increased relative to those in control cells, a result consistent with an unexpected enhancement in the migration of single β-PIX knockdown cells and monolayers of such cells. We propose that targeting β-PIX might be a means of promoting epithelialization of wounds in vivo.

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“…Importantly, kinetic analyses have recently demonstrated the involvement of myosin II in the timely maturation of FX and FA. 7,10,11 The biological mechanisms deciphering how myosin II functions in FA maturation remain to be fully unraveled, but could be through either the generation of tension, which directly affects the conformation of proteins in the adhesion complex 12 or its cross-linking activity. 11,13 Consequently, factors that can regulate both myosin II's cross-linking activities and contraction are good candidates to govern FA formation.…”

Section: S100a4 Downregulates Filopodia Formation Through Increased Dmentioning

confidence: 99%

“…Such possibility is supported by recent findings demonstrating the importance of myosin II in the timely maturation of focal complexes (FX) and FA. 7,10,11 Such lack of maturation would, therefore, lead to filopodial retraction and a low number of FAs resulting in the observed effects on morphology and migration. The reasons for S100A4 to induce such effects through myosin IIA remain to be explicitly demonstrated.…”

confidence: 99%