Cross-talk between integrins α1β1 and α2β1 in renal epithelial cells

The collagen-binding integrins alpha 1 beta 1 and alpha 2 beta 1 have profoundly different functions, yet they are often co-expressed in epithelial cells. When both integrins are expressed in the same cell, it has been suggested that alpha 1 beta 1 negatively regulates integrin alpha 2 beta 1-dependent functions. In this study we utilized murine ureteric bud (UB) epithelial cells, which express no functionally detectable levels of endogenous integrins alpha 1 beta 1 and alpha 2 beta 1, to determine the mechanism whereby this regulation Occurs. We demonstrate that UB cells expressing integrin alpha 2 beta 1, but not alpha 1 beta 1 adhere, migrate and proliferate on collagen I as well as form cellular cords in 3D collagen I gels. Substitution of the transmembrane domain of the integrin alpha 2 subunit with that of alpha 1 results in decreased cell adhesion, migration and cord formation. in contrast, substitution of the integrin alpha 2 cytoplasmic tail with that of alpha 1, decreases cell migration and cord formation, but increases proliferation. When integrin alpha 1 and alpha 2 subunits are co-expressed in UB cells, the alpha 1 subunit negatively regulates integrin alpha 2 beta 1-dependent cord formation, adhesion and migration and this inhibition requires expression of both alpha 1 and alpha 2 tails. Thus, we provide evidence that the transmembrane and cytoplasmic domains of the alpha 2 integrin subunit, as well as the alpha 1 integrin subunit, regulate integrin alpha 2 beta 1 cell function. (C) 2008 Elsevier Inc. All rights reserved.