The selective regulation of α vβ 1 integrin expression is based on the hierarchical formation of α v-containing heterodimers

Abstract

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