Cross-talk between integrins alpha1beta1 and alpha2beta1 in renal epithelial cells.
The collagen-binding integrins alpha1beta1 and alpha2beta1 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 alpha1beta1 negatively regulates integrin alpha2beta1-dependent functions. In this study we utilized murine ureteric bud (UB) epithelial cells, which express no functionally detectable levels of endogenous integrins alpha1beta1 and alpha2beta1, to determine the mechanism whereby this regulation occurs. We demonstrate that UB cells expressing integrin alpha2beta1, but not alpha1beta1 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 alpha2 subunit with that of alpha1 results in decreased cell adhesion, migration and cord formation. In contrast, substitution of the integrin alpha2 cytoplasmic tail with that of alpha1, decreases cell migration and cord formation, but increases proliferation. When integrin alpha1 and alpha2 subunits are co-expressed in UB cells, the alpha1 subunit negatively regulates integrin alpha2beta1-dependent cord formation, adhesion and migration and this inhibition requires expression of both alpha1 and alpha2 tails. Thus, we provide evidence that the transmembrane and cytoplasmic domains of the alpha2 integrin subunit, as well as the alpha1 integrin subunit, regulate integrin alpha2beta1 cell function.
Abair
Tristin D
TD
Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, TN 37232, USA.
Sundaramoorthy
Munirathinam
M
Chen
Dong
D
Heino
Jyrki
J
Ivaska
Johanna
J
Hudson
Billy G
BG
Sanders
Charles R
CR
Pozzi
Ambra
A
Zent
Roy
R
D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism*; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction
D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1