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Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement.

Yoshigi M, Hoffman LM, Jensen CC, Yost HJ, Beckerle MC - J. Cell Biol. (2005)

Bottom Line: Organs and tissues adapt to acute or chronic mechanical stress by remodeling their actin cytoskeletons.Cells that are stimulated by cyclic stretch or shear stress in vitro undergo bimodal cytoskeletal responses that include rapid reinforcement and gradual reorientation of actin stress fibers; however, the mechanism by which cells respond to mechanical cues has been obscure.Our findings identify zyxin as a mechanosensitive protein and provide mechanistic insight into how cells respond to mechanical cues.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. masaaki.yoshigi@hsc.utah.edu

ABSTRACT
Organs and tissues adapt to acute or chronic mechanical stress by remodeling their actin cytoskeletons. Cells that are stimulated by cyclic stretch or shear stress in vitro undergo bimodal cytoskeletal responses that include rapid reinforcement and gradual reorientation of actin stress fibers; however, the mechanism by which cells respond to mechanical cues has been obscure. We report that the application of either unidirectional cyclic stretch or shear stress to cells results in robust mobilization of zyxin from focal adhesions to actin filaments, whereas many other focal adhesion proteins and zyxin family members remain at focal adhesions. Mechanical stress also induces the rapid zyxin-dependent mobilization of vasodilator-stimulated phosphoprotein from focal adhesions to actin filaments. Thickening of actin stress fibers reflects a cellular adaptation to mechanical stress; this cytoskeletal reinforcement coincides with zyxin mobilization and is abrogated in zyxin- cells. Our findings identify zyxin as a mechanosensitive protein and provide mechanistic insight into how cells respond to mechanical cues.

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Cyclic stretch induces zyxin mobilization from focal adhesions to the actin cytoskeleton. (A) Fibroblasts on unstretched membranes (−) or subjected to uniaxial cyclic stretch (+; 1 h at 15% and 0.5 Hz) aligned and reinforced their actin filaments (phalloidin staining), whereas the focal adhesion protein vinculin remained at adhesion sites. (B) In contrast to vinculin, unidirectional cyclic stretch resulted in the mobilization of zyxin from focal adhesions to actin filaments. (C) Double labeling of vinculin and zyxin revealed their colocalization at focal adhesions in unstretched cells. Detection of vinculin in focal adhesions of stretched cells in which zyxin has been mobilized to actin filaments clearly illustrates that focal adhesions persist after stretch and highlight the reduced zyxin levels at those sites.
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fig2: Cyclic stretch induces zyxin mobilization from focal adhesions to the actin cytoskeleton. (A) Fibroblasts on unstretched membranes (−) or subjected to uniaxial cyclic stretch (+; 1 h at 15% and 0.5 Hz) aligned and reinforced their actin filaments (phalloidin staining), whereas the focal adhesion protein vinculin remained at adhesion sites. (B) In contrast to vinculin, unidirectional cyclic stretch resulted in the mobilization of zyxin from focal adhesions to actin filaments. (C) Double labeling of vinculin and zyxin revealed their colocalization at focal adhesions in unstretched cells. Detection of vinculin in focal adhesions of stretched cells in which zyxin has been mobilized to actin filaments clearly illustrates that focal adhesions persist after stretch and highlight the reduced zyxin levels at those sites.

Mentions: To explore whether the molecular composition of the focal adhesion is modulated in response to physical force, we characterized the subcellular localization of a number of focal adhesion constituents in response to cyclic stretch. After stretch for 15 min–1 h, vinculin-containing focal adhesions increased in number and size (Fig. 2 A), which is consistent with previous reports that mechanical force induces the remodeling of integrin-based adhesions (Davies et al., 1994; Mack et al., 2004). Like vinculin, many other focal adhesion constituents, including paxillin, talin, and FAK, remained concentrated in focal adhesions of both unstretched and stretched cells (unpublished data). In striking contrast to vinculin, the focal adhesion protein zyxin was rapidly mobilized from focal adhesions to the remodeling actin filaments in response to cyclic stretch (Fig. 2 B). We obtained similar results with multiple, independently derived antizyxin antibodies (not depicted). Double labeling of vinculin and zyxin clearly revealed that vinculin-rich focal adhesions remained intact even as zyxin displayed a dramatic redistribution to actin filaments (Fig. 2 C). In a recent study in which vascular smooth muscle cells were stretched equibiaxially, zyxin moved from focal adhesions to cell nuclei, but no accumulation of zyxin on actin filaments was reported (Cattaruzza et al., 2004). The variance may be a result of differences in cell type or of the protocols used for mechanical stimulation.


Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement.

Yoshigi M, Hoffman LM, Jensen CC, Yost HJ, Beckerle MC - J. Cell Biol. (2005)

Cyclic stretch induces zyxin mobilization from focal adhesions to the actin cytoskeleton. (A) Fibroblasts on unstretched membranes (−) or subjected to uniaxial cyclic stretch (+; 1 h at 15% and 0.5 Hz) aligned and reinforced their actin filaments (phalloidin staining), whereas the focal adhesion protein vinculin remained at adhesion sites. (B) In contrast to vinculin, unidirectional cyclic stretch resulted in the mobilization of zyxin from focal adhesions to actin filaments. (C) Double labeling of vinculin and zyxin revealed their colocalization at focal adhesions in unstretched cells. Detection of vinculin in focal adhesions of stretched cells in which zyxin has been mobilized to actin filaments clearly illustrates that focal adhesions persist after stretch and highlight the reduced zyxin levels at those sites.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171187&req=5

fig2: Cyclic stretch induces zyxin mobilization from focal adhesions to the actin cytoskeleton. (A) Fibroblasts on unstretched membranes (−) or subjected to uniaxial cyclic stretch (+; 1 h at 15% and 0.5 Hz) aligned and reinforced their actin filaments (phalloidin staining), whereas the focal adhesion protein vinculin remained at adhesion sites. (B) In contrast to vinculin, unidirectional cyclic stretch resulted in the mobilization of zyxin from focal adhesions to actin filaments. (C) Double labeling of vinculin and zyxin revealed their colocalization at focal adhesions in unstretched cells. Detection of vinculin in focal adhesions of stretched cells in which zyxin has been mobilized to actin filaments clearly illustrates that focal adhesions persist after stretch and highlight the reduced zyxin levels at those sites.
Mentions: To explore whether the molecular composition of the focal adhesion is modulated in response to physical force, we characterized the subcellular localization of a number of focal adhesion constituents in response to cyclic stretch. After stretch for 15 min–1 h, vinculin-containing focal adhesions increased in number and size (Fig. 2 A), which is consistent with previous reports that mechanical force induces the remodeling of integrin-based adhesions (Davies et al., 1994; Mack et al., 2004). Like vinculin, many other focal adhesion constituents, including paxillin, talin, and FAK, remained concentrated in focal adhesions of both unstretched and stretched cells (unpublished data). In striking contrast to vinculin, the focal adhesion protein zyxin was rapidly mobilized from focal adhesions to the remodeling actin filaments in response to cyclic stretch (Fig. 2 B). We obtained similar results with multiple, independently derived antizyxin antibodies (not depicted). Double labeling of vinculin and zyxin clearly revealed that vinculin-rich focal adhesions remained intact even as zyxin displayed a dramatic redistribution to actin filaments (Fig. 2 C). In a recent study in which vascular smooth muscle cells were stretched equibiaxially, zyxin moved from focal adhesions to cell nuclei, but no accumulation of zyxin on actin filaments was reported (Cattaruzza et al., 2004). The variance may be a result of differences in cell type or of the protocols used for mechanical stimulation.

Bottom Line: Organs and tissues adapt to acute or chronic mechanical stress by remodeling their actin cytoskeletons.Cells that are stimulated by cyclic stretch or shear stress in vitro undergo bimodal cytoskeletal responses that include rapid reinforcement and gradual reorientation of actin stress fibers; however, the mechanism by which cells respond to mechanical cues has been obscure.Our findings identify zyxin as a mechanosensitive protein and provide mechanistic insight into how cells respond to mechanical cues.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. masaaki.yoshigi@hsc.utah.edu

ABSTRACT
Organs and tissues adapt to acute or chronic mechanical stress by remodeling their actin cytoskeletons. Cells that are stimulated by cyclic stretch or shear stress in vitro undergo bimodal cytoskeletal responses that include rapid reinforcement and gradual reorientation of actin stress fibers; however, the mechanism by which cells respond to mechanical cues has been obscure. We report that the application of either unidirectional cyclic stretch or shear stress to cells results in robust mobilization of zyxin from focal adhesions to actin filaments, whereas many other focal adhesion proteins and zyxin family members remain at focal adhesions. Mechanical stress also induces the rapid zyxin-dependent mobilization of vasodilator-stimulated phosphoprotein from focal adhesions to actin filaments. Thickening of actin stress fibers reflects a cellular adaptation to mechanical stress; this cytoskeletal reinforcement coincides with zyxin mobilization and is abrogated in zyxin- cells. Our findings identify zyxin as a mechanosensitive protein and provide mechanistic insight into how cells respond to mechanical cues.

Show MeSH
Related in: MedlinePlus