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Originally published as MBC in Press, 10.1091/mbc.E07-06-0582 on September 5, 2007

Vol. 18, Issue 11, 4519-4527, November 2007

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Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical SignalsFormula Formula

Wei-hui Guo, and Yu-li Wang

Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01605

Submitted June 19, 2007; Revised August 9, 2007; Accepted August 27, 2007
Monitoring Editor: Carole Parent

Recent studies suggest that mechanical signals mediated by the extracellular matrix play an essential role in various physiological and pathological processes; yet, how cells respond to mechanical stimuli remains elusive. Using live cell fluorescence imaging, we found that actin filaments, in association with a number of focal adhesion proteins, including zyxin and vasodilator-stimulated phosphoprotein, undergo retrograde fluxes at focal adhesions in the lamella region. This flux is inversely related to cell migration, such that it is amplified in fibroblasts immobilized on micropatterned islands. In addition, the flux is regulated by mechanical signals, including stretching forces applied to flexible substrates and substrate stiffness. Conditions favoring the flux share the common feature of causing large retrograde displacements of the interior actin cytoskeleton relative to the substrate anchorage site, which may function as a switch translating mechanical input into chemical signals, such as tyrosine phosphorylation. In turn, the stimulation of actin flux at focal adhesions may function as part of a feedback mechanism, regulating structural assembly and force production in relation to cell migration and mechanical load. The retrograde transport of associated focal adhesion proteins may play additional roles in delivering signals from focal adhesions to the interior of the cell.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-06-0582) on September 5, 2007.

Formula Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Yu-li Wang (yuli.wang{at}umassmed.edu).

Abbreviations used: FAK, focal adhesion kinase; FRAP, fluorescence recovery after photobleaching; VASP, vasodilator-stimulated phosphoprotein.







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