Journal of Biological Chemistry
Volume 276, Issue 47, 23 November 2001, Pages 43860-43870
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MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
Ligation of Integrin α3β1 by Laminin 5 at the Wound Edge Activates Rho-dependent Adhesion of Leading Keratinocytes on Collagen*

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Wounding of the epidermis signals the transition of keratinocytes from quiescent anchorage on endogenous basement membrane laminin 5 to migration on exposed dermal collagen. In this study, we attempt to characterize activation signals that transform quiescent keratinocytes into migratory leading cells at the wound edge. Previously, we reported that adhesion and spreading on collagen via integrin α2β1 by cultured human foreskin keratinocytes (HFKs) requires RhoGTP, a regulator of actin stress fibers. In contrast, adhesion and spreading on laminin 5 requires integrins α3β1 and α6β4 and is dependent on phosphoinositide 3-hydroxykinase (Nguyen, B. P., Gil, S. G., and Carter, W. G. (2000) J. Biol. Chem. 275, 31896–31907). Here, we report that quiescent HFKs do not adhere to collagen but adhere and spread on laminin 5. By using collagen adhesion as one criterion for conversion to a “leading wound cell,” we found that activation of collagen adhesion requires elevation of RhoGTP. Adhesion of quiescent HFKs to laminin 5 via integrin α3β1 and α6β4is sufficient to increase levels of RhoGTP required for adhesion and spreading on collagen. Consistently, adhesion of quiescent HFKs to laminin 5, but not collagen, also promotes expression of the precursor form of laminin 5, a characteristic of leading keratinocytes in the epidermal outgrowth. We suggest that wounding of quiescent epidermis initiates adhesion and spreading of keratinocytes at the wound edge on endogenous basement membrane laminin 5 via α3β1 and α6β4in a Rho-independent mechanism. Spreading on endogenous laminin 5 via α3β1 is necessary but not sufficient to elevate expression of precursor laminin 5 and RhoGTP, allowing for subsequent collagen adhesion via α2β1, all characteristics of leading keratinocytes in the epidermal outgrowth.

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Published, JBC Papers in Press, September 24, 2001, DOI 10.1074/jbc.M103404200

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This work was support by National Institute of Health Grants CA49259 and AR21557 (to W. G. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.