Interaction of the disintegrin and cysteine-rich domains of ADAM12 with integrin α7β1

Abstract

We describe a novel interaction between the disintegrin and cysteine-rich (DC) domains of ADAM12 and the integrin α7β1. Integrin α7β1 extracted from human embryonic kidney 293 cells transfected with α7 cDNA was retained on an affinity column containing immobilized DC domain of ADAM12. 293 cells stably transfected with α7 cDNA adhered to DC-coated wells, and this adhesion was partially inhibited by 6A11 integrin α7 function-blocking antibody. The X1 and the X2 extracellular splice variants of integrin α7 supported equally well adhesion to the DC protein. Integrin α7β1-mediated cell adhesion to DC had different requirements for Mn 2+ than adhesion to laminin. Furthermore, integrin α7β1-mediated cell adhesion to laminin, but not to DC, resulted in efficient cell spreading and phosphorylation of focal adhesion kinase (FAK) at Tyr397. We also show that adhesion of L6 myoblasts to DC is mediated in part by the endogenous integrin α7β1 expressed in these cells. Since integrin α7 plays an important role in muscle cell growth, stability, and survival, and since ADAM12 has been implicated in muscle development and regeneration, we postulate that the interaction between ADAM12 and integrin α7β1 may be relevant to muscle development, function, and disease. We also conclude that laminin and the DC domain of ADAM12 represent two functional ligands for integrin α7β1, and adhesion to each of these two ligands via integrin α7β1 triggers different cellular responses.