THE HUMAN INTEGRIN ALPHA-8-BETA-1 FUNCTIONS AS A RECEPTOR FOR TENASCIN, FIBRONECTIN, AND VITRONECTIN

The integrin family of adhesion receptors consists of at least 21 hete rodimeric transmembrane proteins that differ in their tissue distribut ion and ligand specificity. The recently identified alpha 8 integrin s ubunit associates with beta 1 and is predominantly expressed in smooth muscle and other contractile cells in adult tissues, and in mesenchym al and neural cells during development, We now show that alpha 8 beta 1 specifically localizes to focal contacts in cells plated on the extr acellular matrix proteins fibronectin or vitronectin, In addition we s how that human embryonic kidney cells (293), transfected with alpha 8 cDNA, express alpha 8 beta 1 on their surface and use this recep tor f or adhesion to fibronectin and vitronectin. Furthermore, alpha 8 beta 1 binds to both fibronectin- and vitronectin-Sepharose and can be spec ifically eluted from either matrix protein by the arginine-glycine-asp artic acid (RGD)-containing peptide, GRGDSP. Because fibronectin and v itronectin adhesion appeared to be mediated by RGD, we examined additi onal RGD-containing proteins, including tenascin, fibrinogen, thrombos pondin, osteopontin, and denatured collagen type I. We found that only tenascin was able to mediate adhesion of alpha 8-transfected 293 cell s, By using recombinant fragments of tenascin in adhesion assays, we w ere able to localize the alpha 8 beta 1 binding domain of tenascin to the RGD-containing, third fibronectin type III repeat. These data stro ngly suggest that tenascin, fibronectin, and vitronectin are Ligands f or alpha 8 beta 1 and that this integrin binds to the RGD site in each of these ligands through mechanisms that are distinct and separate fr om alpha 5-and alpha v-containing integrins.