Growth cone collapse through coincident loss of actin bundles and leading edge actin without actin depolymerization

Repulsive guidance cues can either collapse the whole growth cone to arrest neurite outgrowth or cause asymmetric collapse leading to growth cone turn ing. How signals from repulsive cues are translated by growth cones into th is morphological change through rearranging the cytoskeleton is unclear. We examined three factors that are able to induce the collapse of extending H elisoma growth cones in conditioned medium, including serotonin, myosin lig ht chain kinase inhibitor, and phorbol ester. To study the cytoskeletal eve nts contributing to collapse, we cultured Helisoma growth cones on polylysi ne in which lamellipodial collapse was prevented by substrate adhesion. We found that all three factors that induced collapse of extending growth cone s also caused actin bundle loss in polylysine-attached growth cones without loss of actin meshwork. In addition, actin bundle loss correlated with spe cific filamentous actin redistribution away from the leading edge that is c haracteristic of repulsive factors. Finally, we provide direct evidence usi ng time-lapse studies of extending growth cones that actin bundle loss para lleled collapse. Taken together, these results suggest that actin bundles c ould be a common cytoskeletal target of various collapsing factors, which m ay use different signaling pathways that converge to induce growth cone col lapse.