The integrin α7 cytoplasmic domain regulates cell migration, lamellipodia formation, and p130CAS/Crk coupling

The integrin alpha (7)beta (1) is the major laminin-binding integrin in skeletal, heart, and smooth muscle and is a receptor for laminin-l and -2, It mediates myoblast migration on laminin-l and -2 and thus might be involved in muscle development and repair. Previously we have shown that alpha B-7 as well as the alpha (7)A and -C splice variants induce cell motility on laminin when transfected into nonmotile HEK293 cells. In this study we have investigated the role of the cytoplasmic domain of alpha (7) in the laminin-induced signal transduction of alpha (7)beta (1) integrin regulating cell adhesion and migration. Deletion of the cytoplasmic domain did not affect assembly of the mutated alpha (7)Delta cyt/beta (1) heterodimer on the cell surface or adhesion of alpha (7)Delta cyt-transfected cells to laminin, The motility of these cells on the laminin-1/E8 fragment, however, was significantly reduced to the level of mock-transfected cells; lamellipodia formation and polarization of the cells were also impaired. Adhesion to the laminin-1/E8 fragment induced tyrosine phosphorylation of the focal adhesion kinase, paxillin, and p130(CAS) as well as the formation of a p130(CAS)-Crk complex in wild-type alpha B-7-transfected cells. In alpha B-7 Delta cyt cells, however, the extent of p130(CAS) tyrosine formation was reduced and formation of the p130(CAS)-Crk complex was impaired, with unaltered levels of p130(CAS) and Crk protein levels. These findings indicate adhesion-dependent regulation of p130(CAS)/Crk complex formation by the cytoplasmic domain of alpha B-7 integrin after cell adhesion to laminin-1/E8 and imply alpha B-7-controlled lamellipodia formation and cell migration through the p130(CAS)/Crk protein complex.