G protein subunit Gα13 binds to integrin αIIbβ3 and mediates integrin outside-in signaling

摘要

Integrins mediate cell adhesion to the extracellular matrix and transmit signals within 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 αIIbβ3 and by guanosine triphosphate (GTP)-loading of Gα13. Interference of Gα13 expression or a myristoylated fragment of Gα13 that inhibited interaction of αIIbβ3 with Gα13 diminished activation of protein kinase c-Src and stimulated the small GTPase RhoA, consequently inhibiting cell spreading and accelerating cell retraction. We conclude that integrins are non-canonical Gα13-coupled receptors that provide a mechanism for dynamic regulation of RhoA.