Actin-dependent anterograde movement of growth-cone-like structures along growing hippocampal axons: a novel form of axonal transport?

In time-lapse video recordings of hippocampal neurons in culture, we have identified previously uncharacterized structures, nicknamed "waves," that exhibit lamellipodial activity closely resembling that of growth cones, but which periodically emerge at the base of axons and travel distally at an average rate of 3 microm/min. In electron micrographs of identified waves, the cortical region of the axon appears expanded to either side, forming lamellipodia like those at growth cones. No other gross differences were noted in the ultrastructural features of the axon shaft at the site of a wave. Immunocytochemistry revealed that waves contain a marked concentration of F-actin, GAP-43, cortactin, and ezrin or a related protein, constituents that are also concentrated in growth cones. Treatment with the actin-disrupting agent cytochalasin B caused a reversible collapse of lamellipodia and cessation of the forward movement of individual waves along the axon, indicating that their anterograde transport is dependent on intact actin filaments. Treatment with the microtubule-depolymerizing agent nocodazole led to a rapid disorganization of wave structure and a subsequent suppression of wave activity that may reflect a role of microtubules in actin organization. The results suggest that actin and other cytoskeletal components concentrated in growth cones may be transported together as growth-cone-like structures from the cell body to the axon tip via an actin-dependent mechanism.