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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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Fluid shear stress leads to actin reinforcement, realignment, and mobilization of zyxin and VASP to actin stress fibers. Vascular endothelial cells that were subjected to fluid shear stress (2 h) aligned their actin filaments parallel to the flow direction (arrow). Zyxin and VASP mobilized to actin filaments, whereas vinculin remained at focal adhesions.
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fig4: Fluid shear stress leads to actin reinforcement, realignment, and mobilization of zyxin and VASP to actin stress fibers. Vascular endothelial cells that were subjected to fluid shear stress (2 h) aligned their actin filaments parallel to the flow direction (arrow). Zyxin and VASP mobilized to actin filaments, whereas vinculin remained at focal adhesions.

Mentions: Cyclic stretch experiments have been used to mimic the dynamic environment of the vascular wall, which is expanded by pulsatile pressure (Kakisis et al., 2004). Endothelial cells lining the vascular wall also experience shear stress as a major determinant of endothelial pathophysiology (Cunningham and Gotlieb, 2005). To evaluate whether zyxin mobilization is a general response to mechanical stress or is limited to cyclic stretching, we tested the effect of physiological shear stress (15 dyne/cm2) on zyxin localization. Human umbilical vein endothelial cells that were subjected to laminar shear stress reoriented their actin filaments to align parallel to the fluid flow, as seen by phalloidin staining (Fig. 4). Concomitant with actin realignment, shear stress induced the mobilization of zyxin and VASP onto actin filaments, whereas the focal adhesion protein vinculin was not recruited to stress fibers. Similar results were obtained in human aortic smooth muscle cells upon the application of shear stress (unpublished data). Although the shear-induced accumulation of zyxin and VASP on stress fibers of endothelial cells was apparent, we commonly observed residual zyxin and VASP in focal adhesions as well. The incomplete mobilization of zyxin and VASP may reflect cell type differences or the fact that fluid shear stress represents a milder mechanical stress than cyclic stretch. Together, these data indicate that zyxin and VASP mobilization to stress fibers is a general response to mechanical stress that is conserved in multiple cell types.


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)

Fluid shear stress leads to actin reinforcement, realignment, and mobilization of zyxin and VASP to actin stress fibers. Vascular endothelial cells that were subjected to fluid shear stress (2 h) aligned their actin filaments parallel to the flow direction (arrow). Zyxin and VASP mobilized to actin filaments, whereas vinculin remained at focal adhesions.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Fluid shear stress leads to actin reinforcement, realignment, and mobilization of zyxin and VASP to actin stress fibers. Vascular endothelial cells that were subjected to fluid shear stress (2 h) aligned their actin filaments parallel to the flow direction (arrow). Zyxin and VASP mobilized to actin filaments, whereas vinculin remained at focal adhesions.
Mentions: Cyclic stretch experiments have been used to mimic the dynamic environment of the vascular wall, which is expanded by pulsatile pressure (Kakisis et al., 2004). Endothelial cells lining the vascular wall also experience shear stress as a major determinant of endothelial pathophysiology (Cunningham and Gotlieb, 2005). To evaluate whether zyxin mobilization is a general response to mechanical stress or is limited to cyclic stretching, we tested the effect of physiological shear stress (15 dyne/cm2) on zyxin localization. Human umbilical vein endothelial cells that were subjected to laminar shear stress reoriented their actin filaments to align parallel to the fluid flow, as seen by phalloidin staining (Fig. 4). Concomitant with actin realignment, shear stress induced the mobilization of zyxin and VASP onto actin filaments, whereas the focal adhesion protein vinculin was not recruited to stress fibers. Similar results were obtained in human aortic smooth muscle cells upon the application of shear stress (unpublished data). Although the shear-induced accumulation of zyxin and VASP on stress fibers of endothelial cells was apparent, we commonly observed residual zyxin and VASP in focal adhesions as well. The incomplete mobilization of zyxin and VASP may reflect cell type differences or the fact that fluid shear stress represents a milder mechanical stress than cyclic stretch. Together, these data indicate that zyxin and VASP mobilization to stress fibers is a general response to mechanical stress that is conserved in multiple cell types.

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