The interaction of Gα(13) with integrin β(1) mediates cell migration by dynamic regulation of RhoA

Heterotrimeric G protein Gα(13) is known to transmit G protein–coupled receptor (GPCR) signals leading to activation of RhoA and plays a role in cell migration. The mechanism underlying the role of Gα(13) in cell migration, however, remains unclear. Recently we found that Gα(13) interacts with the cytoplasmic domain of integrin β(3) subunits in platelets via a conserved ExE motif. Here we show that a similar direct interaction between Gα(13) and the cytoplasmic domain of the integrin β(1) subunit plays a critical role in β(1)-dependent cell migration. Point mutation of either glutamic acid in the Gα(13)-binding (767)EKE motif in β(1) or treatment with a peptide derived from the Gα(13)-binding sequence of β(1) abolished Gα(13)–β(1) interaction and inhibited β(1) integrin–dependent cell spreading and migration. We further show that the Gα(13)-β(1) interaction mediates β(1) integrin–dependent Src activation and transient RhoA inhibition during initial cell adhesion, which is in contrast to the role of Gα(13) in mediating GPCR-dependent RhoA activation. These data indicate that Gα(13) plays dynamic roles in both stimulating RhoA via a GPCR pathway and inhibiting RhoA via an integrin signaling pathway. This dynamic regulation of RhoA activity is critical for cell migration on β(1) integrin ligands.