NOVEL ROLES FOR ALPHA-3 BETA-1 INTEGRIN AS A REGULATOR OF CYTOSKELETAL ASSEMBLY AND AS A TRANSDOMINANT INHIBITOR OF INTEGRIN RECEPTOR FUNCTION IN MOUSE KERATINOCYTES

Previously we found that alpha 3 beta 1 integrin-deficient neonatal mi ce develop micro-blisters at the epidermal-dermal junction. These micr o-blisters were associated with poor basement membrane organization. I n the present study we have investigated the effect of alpha 3 beta 1- deficiency on other keratinocyte integrins, actin-associated proteins and F-actin organization. We show that the absence of alpha 3 beta 1 r esults in an increase in stress fiber formation in keratinocytes grown in culture and at the basal face of the basal keratinocytes of alpha 3-null epidermis. Moreover, we see a higher concentration of actin-ass ociated proteins such as vinculin, talin, and alpha-actinin at focal c ontact sites in the alpha 3-deficient keratinocytes. These changes in focal contact composition were not due to a change in steady-state lev els of these proteins, but rather to reorganization due to alpha 3 bet a 1 deficiency. Apart from the loss of alpha 3 beta 1 there is no chan ge in expression of the other integrins expressed by the alpha 3-null keratinocytes. However, in functional assays, alpha 3 beta 1 deficienc y allows an increase in fibronectin and collagen type IV receptor acti vities. Thus, our findings provide evidence for a role of alpha 3 beta 1 in regulating stress fiber formation and as a trans-dominant inhibi tor of the functions of the other integrins in mouse keratinocytes. Th ese results have potential implications for the regulation of keratino cyte adhesion and migration during wound healing.