UMMS Affiliation

Department of Physiology

Publication Date

9-7-2007

Document Type

Article

Subjects

Actins; Animals; *Cell Movement; Focal Adhesions; Metalloproteins; Mice; NIH 3T3 Cells; Phosphotyrosine; Protein-Tyrosine Kinases; *Signal Transduction

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Mol Biol Cell. 2007 Nov;18(11):4519-27. Epub 2007 Sep 5. Link to article on publisher's site

DOI of Published Version

10.1091/mbc.E07-06-0582

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Molecular biology of the cell

PubMed ID

17804814

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