No abstract

CD151, one of the tetraspanins, forms a stable complex with integrin ␣3␤1, the major laminin receptor on the cell surface. We found that 8C3, an anti-CD151 mAb obtained by screening for reactivity with integrin ␣3␤1-CD151 complexes, was capable of dissociating CD151 from integrin ␣3␤1, thereby allowing us to deplete CD151 from purified integrin ␣3␤1-CD151 complexes. The CD151-free integrin ␣3␤1 thus obtained showed a significant reduction in its ability to bind to laminin-10͞11, a high-affinity ligand for integrin ␣3␤1, with a concomitant reduction in its reactivity with mAb AG89, which recognizes activated ␤1-containing integrins. These results raised the possibility that the association of integrin ␣3␤1 with CD151 potentiates the ligand-binding activity of the integrin through sustaining its activated conformation. In support of this possibility, the ligand-binding activity was restored when CD151-free integrin ␣3␤1 was reassociated with purified CD151. 8C3-induced dissociation of CD151 from integrin ␣3␤1 was also demonstrated on the surface of living cells by fluorescent resonance energy transfer imaging, accompanied by a concomitant reduction in the cell adhesion to laminin-10͞11-coated substrates. CD151 knock-down by RNA interference also resulted in a reduction in the adhesive activity of the cells. Taken together, these results indicate that CD151 association modulates the ligandbinding activity of integrin ␣3␤1 through stabilizing its activated conformation not only with purified proteins but also in a physiological context. cell adhesion ͉ laminin