Functional beta1-integrins release the suppression of fibronectin matrix assembly by vitronectin.
beta1-null GD25 fibroblasts adherent to vitronectin fail to bind the N-terminal 70-kDa matrix assembly domain of fibronectin or to assemble fibronectin (Sakai, T., Zhang, Q., Fässler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538). We have made four observations that extend this finding. First, the presence of vitronectin on a substrate that otherwise can support fibronectin assembly has a dominant-negative effect on assembly. Second, the dominant-negative effect is lost when active beta1A is expressed. Third, beta1A containing the extracellular D130A inactivating mutation has a dominant-negative effect on fibronectin assembly. Fourth, beta1-null cells adherent to vitronectin are flat and lack filopodia, whereas beta1-null cells adherent to fibronectin or beta1A-expressing cells adherent to either vitronectin or fibronectin are contracted and exhibit numerous filopodia. These results reveal, therefore, that GD25 cells adherent to vitronectin can only assume a shape suitable for assembly of fibronectin when there is a countervailing signal from functional beta1-integrins.
Zhang
Q
Q
Departments of Medicine and Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Sakai
T
T
Nowlen
J
J
Hayashi
I
I
Fässler
R
R
Mosher
D F
DF
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D015203:Reproducibility of Results; D015398:Signal Transduction; D019096:Vitronectin / Q000378:metabolism*
D005353:Fibronectins; D019012:Integrin beta1; D019096:Vitronectin