Local mechanisms regulating selective cargo entry and long-range trafficking in axons

•Axonal cargo entry depends on the presence of multiple subcompartments in the proximal axon.•Local mechanisms along the axon ensure the long-distance distribution of cargoes.•Microtubule associated proteins regulate motor-dependent axonal trafficking. The polarized long-distance transport of neuronal cargoes depends on the presence of functional and structural axonal subcompartments. Given the heterogeneity of neuronal cargoes, selective sorting and entry occurs in the proximal axon where multiple subcellular specializations such as the axon initial segment, the pre-axonal exclusion zone, the MAP2 pre-axonal filtering zone and the Tau diffusion barrier provide different levels of regulation. Cargoes allowed to pass through the proximal axon spread into the more distal parts. Recent findings show that diverse cargo distributions along the axon depend on the compartmentalized organization of the cytoskeleton and the local regulation of multiple motor proteins by microtubule associated proteins. In this review, we focus on the local mechanisms that control cargo motility and discuss how they play a role in the overall circulation of axonal cargoes.