CDC42 promotes changes in actin cytoskeleton by several pathways.
CDC42 activates PAK1,2,3,4 and CDC42BPA (MRCKalpha) which phosphorylate LIMK1,2.
LIMK1,2 subsquently phosphorylate and inhibit Cofilin
Destrin as actin depolymerizing factor, once phosphorylated by LIMK1,2 is inactive and thus this phosphorylation leads to actin polymerization and stimulation of filopodia and stress fibers formation.
The ARP2_3 complex and Cofilin are involved in protrusion at the leading edge: the actin-severing activity of cofilin and the actin-branching activity of Arp2_3 act in synergy to drive the extension of lamellipodia.
Cofilin is also required for the maintenance of a polarized cytoskeleton and thus for directional cell migration.
Integrins control motile strategy through a Rho-cofilin pathway.
Adhesion to fibronectin by a5b1 integrin leads to phosphorylation and thus inactivation of cofilin.
Cells thus fail to polarize their cytoskeleton but extend thin protrusion with cell-matrix adhesions in multiple directions.