Integrin α chain cytoplasmic tails regulate “antibody‐redirected” cell adhesion, independently of ligand binding

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Abstract
Here we describe a novel “antibody-redirected cell adhesion” (ARCA) assay. This assay measures heterotypic cell-cell adhesion, resulting from antibody bridging between Fcγ receptors type II (CD32) on leukocytes, and clustered intergrins on adherent cell monolayers. This ARCA activity, facilitated by integrins αβ1 or α4β1, required an intact cytoskeleton, but did not involve typical integrin ligand binding sites or divalent cations. Furthermore, deletion of the α4 cytoplasmic tail almost completely abrogated integrin ARCA activity, suggesting an alteration of integrin recruitment into adhesive sites. If two or more tail residues were present after the conserved GFFKR motif, then ARCA activity was largely restored. Although α4 tail deletion caused loss of ARCA activity, it had no effect on the binding of VCAM-1 to intact α4-transfected K562 cells. In conclusion, the integrin α chain tail can positively regulate integrin-dependent cell adhesion by a receptor recruitment/clustering mechanism independent of conventional integrin ligand-binding considerations.