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© The Rockefeller University Press, 0021-9525/1998//1357 $5.00
The Journal of Cell Biology, Volume 142, Number 5, , 1998 1357-1369

Novel Roles for 3β1 Integrin as a Regulator of Cytoskeletal Assembly and as a Trans-dominant Inhibitor of Integrin Receptor Function in Mouse Keratinocytes

Kairbaan M. Hodivala-Dilke^*, C. Michael DiPersio^*, Jordan A. Kreidberg, and Richard O. Hynes^*

^* Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Division of Nephrology and Newborn Medicine, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Previously we found that 3β1 integrin–deficient neonatal mice develop micro-blisters at the epidermal–dermal junction. These micro-blisters were associated with poor basement membrane organization. In the present study we have investigated the effect of 3β1-deficiency on other keratinocyte integrins, actin-associated proteins and F-actin organization. We show that the absence of 3β1 results in an increase in stress fiber formation in keratinocytes grown in culture and at the basal face of the basal keratinocytes of 3-null epidermis. Moreover, we see a higher concentration of actin-associated proteins such as vinculin, talin, and -actinin at focal contact sites in the 3-deficient keratinocytes. These changes in focal contact composition were not due to a change in steady-state levels of these proteins, but rather to reorganization due to 3β1 deficiency. Apart from the loss of 3β1 there is no change in expression of the other integrins expressed by the 3-null keratinocytes. However, in functional assays, 3β1 deficiency allows an increase in fibronectin and collagen type IV receptor activities. Thus, our findings provide evidence for a role of 3β1 in regulating stress fiber formation and as a trans-dominant inhibitor of the functions of the other integrins in mouse keratinocytes. These results have potential implications for the regulation of keratinocyte adhesion and migration during wound healing.

Key Words: 3β1 integrin • trans-dominant inhibition • keratinocyte • wound healing

Abbreviations used in this paper: F-actin, filamentous actin; FN, fibronectin; Coll IV, collagen type IV; LM1 laminin 1, LM5 laminin 5; SAC, stable achoring contact.

The first two authors contributed equally to the work presented.

Please address all correspondence to R.O. Hynes, Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139. Tel.: (617) 253-6422. Fax: (617) 253-8357.

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