Integrin-mediated Signaling via Paxillin-GIT1-PIX Promotes Localized Rac Activation at the Leading Edge and Cell Migration.

Rac activation is precisely regulated temporally and spatially by intracellular signaling pathways in migrating cells to guarantee the formation of specific cell protrusions-lamellipodia at the leading edge. Integrins-mediated adhesions also control the signaling pathway for localized Rac activation in the cells, but very few studies have been addressed in this field. In the study, we aim to focus on how integrin-mediated signaling affects localized Rac activation by reducing the paxillin expression with shRNA targeting paxillin. The results revealed that reduction of the paxillin expression in the cells inhibited the formation of focal adhesions and Rac activation. By using Rac FRET biosensor, Rac activation was localized at the leading edge of the cell, within the lamellipodium. A ternary complex of paxillin-GIT1-PIX could establish the signaling pathway in front of the cells. Thus, we described a mechanism of integrin-mediated signaling for localized Rac activation that upon ligand binding, activated integrin via the signaling pathway paxillin-GIT1-PIX promotes localized Rac activation at the leading edge and cell migration.