The selective regulation of alpha Vbeta 1 integrin expression is based on the hierarchical formation of alpha V-containing heterodimers.
The integrin beta1 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 beta1 subunit is constantly present in a large excess. The expression of several heterodimers containing the alphaV subunit seems to be regulated by an identical mechanism. The fact that many cells express alphaVbeta1 heterodimer, and that this fibronectin/vitronectin receptor may be selectively regulated, compromises the present model of the regulation of beta1 and alphaV 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-alphaV integrin antibody. We could see 70-80% reduction in the cell surface expression of alphaV subunit. However, the only one of the alphaV integrins reduced on the cell surface was alphaVbeta1. This suggests that the cell surface expression level of alphaVbeta1 is dependent on the number of alphaV subunits available after the formation of other alphaV-containing heterodimers. Thus, there seems to be a hierarchy in the complex formation between alphaV and its different beta-partners. These observations explain how alphaVbeta1 can be specifically regulated without concomitant changes in the expression of other alphaV or beta1 integrins.
Koistinen
Pekka
P
MediCity Research Laboratory and the Department of Medical Biochemistry, Turku Graduate School of Biomedical Sciences, University of Turku, FIN-20520 Turku, Finland.
Heino
Jyrki
J
D015703:Antigens, CD / Q000235:genetics*; D002462:Cell Membrane / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D019281:Dimerization; D005353:Fibronectins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039564:Integrin alphaV; D016023:Integrins / Q000235:genetics*; D008545:Melanoma; D008954:Models, Biological; D011485:Protein Binding; D019030:Receptors, Vitronectin; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D005353:Fibronectins; D039564:Integrin alphaV; D016023:Integrins; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; D003094:Collagen