Local self-assembly mechanisms underlie the differential transformation of the proximal and distal cut axonal ends into functional and aberrant growth cones.

Following axotomy, both the proximal and distal cut axonal ends transform into growth cones (GCs). Whereas the GCs formed by the tip of the proximal segment branch to form neurites, the structure formed by the distal cut end fails to grow. The mechanisms underlying the formation of an aberrant GC by the distal cut end are not understood. Earlier we described the cascade that transforms the tip of the proximal cut axon into a GC. This involves microtubule (MT) polar reorientation, which culminates in the formation of two MT-based vesicle traps, one for Golgi-derived vesicles and the other that retains retrogradely transported vesicles. The formation of these traps is the outcome of local interactions between dynamically repolymerizing MTs and molecular motors. The concentration of Golgi-derived vesicles in the plus-end trap is essential for the successful generation of a functional GC. By using online confocal imaging of transected cultured Aplysia neurons, we analyzed here the restructuring of the distal cut end after axotomy. We found that initially the proximal and distal cut ends undergo identical alterations. Nevertheless, in contrast to the proximal end, the distal cut axon forms only a minus-end MT-based trap that concentrates endocytotic vesicles driven by minus-end oriented motors. Whereas the MTs forming the trap polymerize pointing their plus-ends centrifugally to form finger-like protrusions, the trapped vesicles cannot translocate out to fuse with the plasma membrane. Thus, the structure formed at the distal cut axon is incompetent to support growth processes.