Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement
Masaaki Yoshigi3,4,5,
Laura M. Hoffman1,5,
Christopher C. Jensen5,
H. Joseph Yost2,3,5, , and
Mary C. Beckerle1,2,5
1 Department of Biology, University of Utah, Salt Lake City, UT 84112 2 Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112 3 Department of Pediatrics, University of Utah, Salt Lake City, UT 84112 4 Department of Bioengineering, University of Utah, Salt Lake City, UT 84112 5 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112
Correspondence to Mary C. Beckerle: mary.beckerle{at}hci.utah.edu; or Masaaki Yoshigi: masaaki.yoshigi{at}hsc.utah.edu
Abstract:
Organs and tissues adapt to acute or chronic mechanical stressby remodeling their actin cytoskeletons. Cells that are stimulatedby cyclic stretch or shear stress in vitro undergo bimodal cytoskeletalresponses that include rapid reinforcement and gradual reorientationof actin stress fibers; however, the mechanism by which cellsrespond to mechanical cues has been obscure. We report thatthe application of either unidirectional cyclic stretch or shearstress to cells results in robust mobilization of zyxin fromfocal adhesions to actin filaments, whereas many other focaladhesion proteins and zyxin family members remain at focal adhesions.Mechanical stress also induces the rapid zyxin-dependent mobilizationof vasodilator-stimulated phosphoprotein from focal adhesionsto actin filaments. Thickening of actin stress fibers reflectsa cellular adaptation to mechanical stress; this cytoskeletalreinforcement coincides with zyxin mobilization and is abrogatedin zyxin-null cells. Our findings identify zyxin as a mechanosensitiveprotein and provide mechanistic insight into how cells respondto mechanical cues.
M. Yoshigi and L.M. Hoffman contributed equally to this work.
Abbreviations used in this paper: SFTI, stress fiber thicknessindex; VASP, vasodilator-stimulated phosphoprotein.
The editors suggest the following Related Resources on Science sites:
Mechanism of Stretch-Induced Activation of the Mechanotransducer Zyxin in Vascular Cells.
S. Suresh Babu, A. Wojtowicz, M. Freichel, L. Birnbaumer, M. Hecker, and M. Cattaruzza (2012)
Science Signaling
5, ra91
|Abstract »|Full Text »|PDF »
The residence time of focal adhesion kinase (FAK) and paxillin at focal adhesions in renal epithelial cells is determined by adhesion size, strength and life cycle status.
S. E. Le Devedec, B. Geverts, H. de Bont, K. Yan, F. J. Verbeek, A. B. Houtsmuller, and B. van de Water (2012)
J. Cell Sci.
125, 4498-4506
|Abstract »|Full Text »|PDF »
Integrating force-sensing and signaling pathways in a model for the regulation of wing imaginal disc size.
T. Aegerter-Wilmsen, M. B. Heimlicher, A. C. Smith, P. B. de Reuille, R. S. Smith, C. M. Aegerter, and K. Basler (2012)
Development
139, 3221-3231
|Abstract »|Full Text »|PDF »
United we stand - integrating the actin cytoskeleton and cell-matrix adhesions in cellular mechanotransduction.
N. Balanis, M. Yoshigi, M. K. Wendt, W. P. Schiemann, and C. R. Carlin (2011)
Mol. Biol. Cell
22, 4288-4301
|Abstract »|Full Text »|PDF »
Integrins in Cell Migration.
A. Huttenlocher and A. R. Horwitz (2011)
Cold Spring Harb Perspect Biol
3, a005074
|Abstract »|Full Text »|PDF »
Integrin adhesion drives the emergent polarization of active cytoskeletal stresses to pattern cell delamination.
C. Meghana, N. Ramdas, F. M. Hameed, M. Rao, G. V. Shivashankar, and M. Narasimha (2011)
PNAS
108, 9107-9112
|Abstract »|Full Text »|PDF »
Actomyosin-generated tension controls the molecular kinetics of focal adhesions.
H. Wolfenson, A. Bershadsky, Y. I. Henis, and B. Geiger (2011)
J. Cell Sci.
124, 1425-1432
|Abstract »|Full Text »|PDF »
Zyxin Is a Critical Regulator of the Apoptotic HIPK2-p53 Signaling Axis.
J. Crone, C. Glas, K. Schultheiss, J. Moehlenbrink, E. Krieghoff-Henning, and T. G. Hofmann (2011)
Cancer Res.
71, 2350-2359
|Abstract »|Full Text »|PDF »
Integrins and Extracellular Matrix in Mechanotransduction.
Zyxin-mediated Actin Assembly Is Required for Efficient Wound Closure.
T. N. Nguyen, A. Uemura, W. Shih, and S. Yamada (2010)
J. Biol. Chem.
285, 35439-35445
|Abstract »|Full Text »|PDF »
Real-time single-cell response to stiffness.
D. Mitrossilis, J. Fouchard, D. Pereira, F. Postic, A. Richert, M. Saint-Jean, and A. Asnacios (2010)
PNAS
107, 16518-16523
|Abstract »|Full Text »|PDF »
The LIM Protein Zyxin Binds CARP-1 and Promotes Apoptosis.
M. Hervy, L. M. Hoffman, C. C. Jensen, M. Smith, and M. C. Beckerle (2010)
Genes & Cancer
1, 506-515
|Abstract »|Full Text »|PDF »
Zyxin is involved in thrombin signaling via interaction with PAR-1 receptor.
J. Han, G. Liu, J. Profirovic, J. Niu, and T. Voyno-Yasenetskaya (2009)
FASEB J
23, 4193-4206
|Abstract »|Full Text »|PDF »
Single-cell response to stiffness exhibits muscle-like behavior.
D. Mitrossilis, J. Fouchard, A. Guiroy, N. Desprat, N. Rodriguez, B. Fabry, and A. Asnacios (2009)
PNAS
106, 18243-18248
|Abstract »|Full Text »|PDF »
Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding.
A. M. Goldyn, B. A. Rioja, J. P. Spatz, C. Ballestrem, and R. Kemkemer (2009)
J. Cell Sci.
122, 3644-3651
|Abstract »|Full Text »|PDF »
Actin machinery and mechanosensitivity in invadopodia, podosomes and focal adhesions.
C. Albiges-Rizo, O. Destaing, B. Fourcade, E. Planus, and M. R. Block (2009)
J. Cell Sci.
122, 3037-3049
|Abstract »|Full Text »|PDF »
S. Gehler, M. Baldassarre, Y. Lad, J. L. Leight, M. A. Wozniak, K. M. Riching, K. W. Eliceiri, V. M. Weaver, D. A. Calderwood, and P. J. Keely (2009)
Mol. Biol. Cell
20, 3224-3238
|Abstract »|Full Text »|PDF »
Zyxin Mediates Actin Fiber Reorganization in Epithelial-Mesenchymal Transition and Contributes to Endocardial Morphogenesis.
M. Mori, H. Nakagami, N. Koibuchi, K. Miura, Y. Takami, H. Koriyama, H. Hayashi, H. Sabe, N. Mochizuki, R. Morishita, et al. (2009)
Mol. Biol. Cell
20, 3115-3124
|Abstract »|Full Text »|PDF »
Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation.
F. Stanchi, C. Grashoff, C. F. Nguemeni Yonga, D. Grall, R. Fassler, and E. Van Obberghen-Schilling (2009)
J. Cell Sci.
122, 1800-1811
|Abstract »|Full Text »|PDF »
Mechanosensing in actin stress fibers revealed by a close correlation between force and protein localization.
J. Colombelli, A. Besser, H. Kress, E. G. Reynaud, P. Girard, E. Caussinus, U. Haselmann, J. V. Small, U. S. Schwarz, and E. H. K. Stelzer (2009)
J. Cell Sci.
122, 1665-1679
|Abstract »|Full Text »|PDF »
Integrins in cell migration - the actin connection.
M. Vicente-Manzanares, C. K. Choi, and A. R. Horwitz (2009)
J. Cell Sci.
122, 199-206
|Abstract »|Full Text »|PDF »
Mechanical forces facilitate actin polymerization at focal adhesions in a zyxin-dependent manner.
Characteristics of the Phagocytic Cup Induced by Uropathogenic Escherichia coli.
H. Wang, F.-X. Liang, and X.-P. Kong (2008)
Journal of Histochemistry & Cytochemistry
56, 597-604
|Abstract »|Full Text »|PDF »
Paxillin-dependent stimulation of microtubule catastrophes at focal adhesion sites.
A. Efimov, N. Schiefermeier, I. Grigoriev, M. C. Brown, C. E. Turner, J. V. Small, and I. Kaverina (2008)
J. Cell Sci.
121, 196-204
|Abstract »|Full Text »|PDF »
Ena/VASP is required for endothelial barrier function in vivo.
C. Furman, A. L. Sieminski, A. V. Kwiatkowski, D. A. Rubinson, E. Vasile, R. T. Bronson, R. Fassler, and F. B. Gertler (2007)
J. Cell Biol.
179, 761-775
|Abstract »|Full Text »|PDF »
Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical Signals.
Enabled plays key roles in embryonic epithelial morphogenesis in Drosophila.
J. Gates, J. P. Mahaffey, S. L. Rogers, M. Emerson, E. M. Rogers, S. L. Sottile, D. Van Vactor, F. B. Gertler, and M. Peifer (2007)
Development
134, 2027-2039
|Abstract »|Full Text »|PDF »
Flux at Focal Adhesions: Slippage Clutch, Mechanical Gauge, or Signal Depot.
Supervillin modulation of focal adhesions involving TRIP6/ZRP-1.
N. Takizawa, T. C. Smith, T. Nebl, J. L. Crowley, S. J. Palmieri, L. M. Lifshitz, A. G. Ehrhardt, L. M. Hoffman, M. C. Beckerle, and E. J. Luna (2006)
J. Cell Biol.
174, 447-458
|Abstract »|Full Text »|PDF »
Stress fibers are generated by two distinct actin assembly mechanisms in motile cells.