G protein subunit Gα₁₃ binds to integrin α_IIbβ₃ and mediates integrin "outside-in" signaling

Integrins mediate cell adhesion to the extracellular matrix and transmit signals witnin the cell that stimulate cell spreading, retraction, migration, and proliferation. The mechanism of integrin outside-in signaling has been unclear. We found that the heterotrimeric guanine nucleotide-binding protein (G protein) Gα₁₃ directly bound to the integrin β₃ cytoplasmic domain and that Gα₁₃-integrin interaction was promoted by ligand binding to the integrin α_IIbβ ₃ and by guanosine triphosphate (GTP) loading of Gα ₁₃. Interference of Gα₁₃ expression or a myristoylated fragment of Gα₁₃ that inhibited interaction of α_IIbβ₃ with Gα₁₃ diminished activation of protein kinase c-Src and stimulated the small guanosine triphosphatase RhoA, consequently inhibiting cell spreading and accelerating cell retraction. We conclude that integrins are noncanonical Gα₁₃-coupled receptors that provide a mechanism for dynamic regulation of RhoA.