Fig. 8.

Model of endocytic organelle traffic in axons. Material enters the growth cone, where it most likely acidifies slightly and encounters sorting and recycling machinery. From here, an important sorting event takes place (1). Perhaps by budding from a sorting compartment (a) or by direct transport from the plasma membrane (b), a subset of the endocytosed material is sent retrogradely out of the growth cone into the distal part of the axon shaft. After these neutral organelles have been transported some distance from the growth cone, they encounter another important transition point where many of them acidify (2). The high concentration of LEP100 in this region suggests that the incoming endocytic organelles are encountering anterogradely moving vesicles delivering macromolecular components involved in progression through the degradative endosomal–lysosomal pathway. From here they continue their retrograde journey and often encounter branch points (3), another region where significant organelle acidification might occur and encounters with anterogradely moving delivery vesicles might take place. By the time they reach the cell body, most of the endocytic organelles are acidified and are well into the degradative endosomal–lysosomal pathway. However, a small fraction of organelles do remain neutral at this point and likely represent those that are necessarily excluded from the degradative pathway.