FIGURE 9:

Model for Src/cortactin-mediated regulation of dynamics and morphology of growth cone lamellipodia and filopodia. Schematic depicting leading edge of lamellipodia and filopodia of neuronal growth cone in control condition (left), with up-regulated Src activation and cortactin levels (middle), and with down-regulated Src activation and cortactin tyrosine phosphorylation levels (right). 1) In lamellipodia, Src phosphorylation of cortactin facilitates Arp2/3 complex–dependent actin nucleation and branching, which results in lamellipodial protrusion. 2) Src and cortactin contribute to filopodia formation and positioning within the actin network by facilitating Arp2/3-mediated actin branch formation and stabilization. 3) In filopodia, Src phosphorylation of cortactin stabilizes bundles of actin filaments, resulting in straight filopodia. 4) Src and cortactin regulate the transition between different states of actin assembly at the plus end of filaments, thereby controlling persistence of protrusions. High rates of assembly occur during protrusion, whereas low rates of assembly occur during retraction. Up-regulation of Src activation and cortactin levels results in longer filopodia and lamellipodia, higher density of filopodia and actin network in lamellipodia, and more persistent actin-driven protrusions (middle). Down-regulation of Src activation and cortactin phosphorylation results in shorter filopodia and lamellipodia, reduced density of filopodia and actin network in lamellipodia, less persistent protrusions, and increased lateral movements of filopodia (right).