The selective regulation of αvβ1 integrin expression is based on the hierarchical formation of αv-containing heterodimers

The integrin beta(1) subunit can form a heterodimer with 12 different alpha subunits. According to the present model, the expression level of any alphabeta complex is regulated by the availability of the specific alpha subunit, whereas beta(1) subunit is constantly present in a large excess. The expression of several heterodimers containing the alpha(V) subunit seems to be regulated by an identical mechanism. The fact that many cells express alpha(V)beta(1) heterodimer, and that this fibronectin/vitronectin receptor may be selectively regulated, compromises the present model of the regulation of beta(1) and alpha(V) integrins. We have tried to solve this problem by assuming that distinct alphabeta heterodimers are formed with different tendency. To test the hypothesis, we analyzed WM-266-4 melanoma cells transfected with a cDNA construct coding for an intracellular single-chain anti-alpha(V) integrin antibody. We could see 70-80% reduction in the cell surface expression of alpha(V) subunit. However, the only one of the alpha(V) integrins reduced on the cell surface was alpha(V)beta(1). This suggests that the cell surface expression level of alpha(V)beta(1) is dependent on the number of alpha(V) subunits available after the formation of other alpha(V)-containing heterodimers. Thus, there seems to be a hierarchy in the complex formation between alpha(V) and its different beta-partners. These observations explain how alpha(V)beta(1) can be specifically regulated without concomitant changes in the expression of other alpha(V) or beta(1) integrins.