Cross-talk between integrins {alpha}1{beta}1 and {alpha}2{beta}1 in renal epithelial cells
- Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, TN 37232 (United States)
- Department of Biochemistry and Food Chemistry, University of Turku, Turku (Finland)
- VTT Technical Research Centre of Finland, Medical Biotechnology, Turku (Finland)
- Department of Biochemistry, Vanderbilt University, Nashville, TN 37232 (United States)
- Department of Medicine, Veterans Affairs Hospital, Nashville, TN 37232 (United States)
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.
- OSTI ID:
- 21176144
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 19 Vol. 314; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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