RGD-independent binding of integrin alpha(9)beta(1) to the ADAM-12 and-15 disintegrin domains mediates cell-cell interaction

ADAMs (a disintegrin and metalloproteases) mediate several important proces ses (e.g. tumor necrosis factor-cy:release, fertilization, and myoblast fus ion). The ADAM disintegrin domains generally lack RGD motifs, and their rec eptors are virtually unknown. Here we show that integrin alpha (9)beta (1) specifically interacts with the recombinant ADAMs-12 and -15 disintegrin do mains in an RGD-independent manner. We also show that interaction between A DAM-12 or -15 and alpha (9)beta (1) supports cell-cell interaction Interest ingly, the cation requirement and integrin activation status required for a lpha (9)beta (1)/ADAM-mediated cell adhesion and cell-cell interaction is s imilar to those required for known integrin-extracellular matrix interactio n. These results are quite different from recent reports that ADAM-2/alpha (6)beta (1) interaction during sperm/egg fusion requires an integrin activa tion status distinct from that for extracellular matrix interaction. These results suggest that alpha (9)beta (1) may be a major receptor for ADAMs th at lack RGD motifs, and that, considering a wide distribution of ADAMs and alpha (9)beta (1), this interaction may be of potential biological and path ological significance.