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Published online
doi:10.1083/jcb.200608010
The Journal of Cell Biology, Vol. 176, No. 5, 667-680
The Rockefeller University Press, 0021-9525 $30.00
© Schober et al.
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Article

Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics



Markus Schober1, Srikala Raghavan1, Maria Nikolova1, Lisa Polak1, H. Amalia Pasolli1, Hilary E. Beggs2, Louis F. Reichardt2, and Elaine Fuchs1

1 Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
2 Department of Physiology, University of California, San Francisco, San Francisco, CA 94143

Correspondence to Elaine Fuchs: fuchs{at}rockefeller.edu

In response to {alpha}ß1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable for epidermal adhesion and basement membrane assembly, both of which require {alpha}ß1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of {alpha}ß1 integrin in regulating cytoskeletal dynamics and orchestrating polarized keratinocyte migration out of epidermal explants. Fak-null keratinocytes display an aberrant actin cytoskeleton, which is tightly associated with robust, peripheral focal adhesions and microtubules. We find that without FAK, Src, p190RhoGAP, and PKL–PIX–PAK, localization and/or activation at focal adhesions are impaired, leading to elevated Rho activity, phosphorylation of myosin light chain kinase, and enhanced tensile stress fibers. We show that, together, these FAK-dependent activities are critical to control the turnover of focal adhesions, which is perturbed in the absence of FAK.

S. Raghavan's present address is College of Dental Medicine and Department of Dermatology, Columbia University, New York, NY 10032.

Abbreviations used in this paper: cKO, conditional KO; FA, focal adhesion; FN, fibronectin; GAP, GTPase-activating protein; ILK, integrin-linked kinase; KO, knockout; MK, mouse keratinocyte; MLC, myosin light chain; MYPT, myosin phosphatase target; PAK, p21-activated kinase; PIX, PAK-interacting exchange factor; PKL, p95 paxillin kinase linker; PXN, paxillin; PYK2, proline-rich tyrosine kinase 2; ROCK, Rho kinase; VIN, vinculin; WT, wild-type.


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