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Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover
X D Ren1, W B Kiosses, D J Sieg
1Departments of Vascular Biology and Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Abstract:
Focal adhesion kinase (FAK) is activated and localized at focal adhesions upon cell adhesion to extracellular matrices. Cells lacking FAK show increased focal adhesion number and decreased cell migration, functions that are regulated by the small GTPase Rho. We now report that fibroblasts from FAK-/- mice failed to transiently inhibit Rho activity when plated on fibronectin. Re-expression of FAK restored normal Rho regulation. Turnover of focal adhesions correlated inversely with Rho activity. The presence or absence of FAK was mimicked by inhibiting or activating Rho, respectively. These data suggest that loss of FAK resulting in constitutive activation of Rho and inhibition of focal adhesion turnover can account for deficiencies in cell migration and embryonic lethality of the FAK knockout.
Insights
Focal adhesion kinase (FAK) regulates cell migration by controlling Rho activity. Loss of FAK leads to persistent Rho activation, hindering focal adhesion turnover and causing migration defects.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Focal adhesion kinase (FAK) plays a crucial role in cell adhesion and migration.
- FAK is activated at focal adhesions upon binding to extracellular matrices.
- The small GTPase Rho regulates cell migration and focal adhesion dynamics.
Purpose of the Study:
- To investigate the role of FAK in regulating Rho activity.
- To understand the mechanism by which FAK influences cell migration.
- To elucidate the cause of embryonic lethality in FAK knockout mice.
Main Methods:
- Analysis of FAK-deficient (FAK-/-) mouse fibroblasts.
- Assessment of Rho activity upon plating on fibronectin.
- Evaluation of focal adhesion turnover.
- Re-expression of FAK in FAK-/- cells.
Main Results:
- FAK-/- fibroblasts exhibited a failure to transiently inhibit Rho activity.
- Re-expression of FAK restored normal Rho regulation.
- Focal adhesion turnover was inversely correlated with Rho activity.
- Inhibiting or activating Rho mimicked the presence or absence of FAK, respectively.
Conclusions:
- Loss of FAK leads to constitutive Rho activation.
- Constitutive Rho activation inhibits focal adhesion turnover.
- These FAK-dependent Rho dysregulations account for impaired cell migration and embryonic lethality in FAK knockout models.