title: Cross-talk between integrins alpha1beta1 and alpha2beta1 in renal epithelial cells.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Tristin D
authors.initials: TD
authors.lastname: Abair
authors.forename: Munirathinam
authors.initials: M
authors.lastname: Sundaramoorthy
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heino
authors.forename: Johanna
authors.initials: J
authors.lastname: Ivaska
authors.forename: Billy G
authors.initials: BG
authors.lastname: Hudson
authors.forename: Charles R
authors.initials: CR
authors.lastname: Sanders
authors.forename: Ambra
authors.initials: A
authors.lastname: Pozzi
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
mesh_terms: 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
chemical_list: D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1