Cellular and molecular mechanisms underlying srGAP2 function during neuronal development

During brain development, proper neuronal migration and morphogenesis is critical for the establishment of functional neuronal circuits. I have identified that srGAP2 negatively regulates neuronal migration and induces both neurite outgrowth and branching through the ability of its F-BAR domain to induce filopodia-like membrane protrusions resembling those induced by I-BAR domains in vivo and in vitro. Previous work has suggested that in non-neuronal cells, forced expression of proteins that promote filopodia decrease the rate of cell migration and the persistence of leading edge protrusions. srGAP2 knockdown reduces leading process branching and increases the rate of neuronal migration in vivo. Overexpression of srGAP2 or its F-BAR domain has the opposite effects, increasing leading process branching and dynamics and blocking migration. Finally, expression of a truncated form of the F-BAR domain that localizes to the membrane but fails to elicit filopodia-like membrane protrusions does not inhibit neuronal migration. This work highlights the functional importance of proteins directly regulating membrane deformation for proper neuronal migration and morphogenesis.