Src and Cortactin Regulate Actin Organization and Dynamics in Neuronal Growth Cone Lamellipodia and Filopodia

Src tyrosine kinases have been implicated in axonal growth and guidance; however, the underlying cellular mechanisms are not well understood. Here, I investigated the function of Src2 and one of its substrates, cortactin, in regulating the morphology and motility of Aplysia growth cones. I found that up-regulation of Src2 activation state or cortactin increased lamellipodia length, protrusion time, and actin network density, whereas down-regulation had opposite effects. Furthermore, Src2 or cortactin up-regulation increased filopodia density, length, and protrusion time, whereas down-regulation promoted lateral movements of filopodia. Fluorescent speckle microscopy revealed that rates of actin assembly and retrograde flow were not affected in either case. These results suggest that Src and cortactin regulate growth cone motility by increasing actin network density and protrusion persistence of lamellipodia as well as the formation and stability of actin bundles in filopodia.