The axonal endoplasmic reticulum and protein trafficking: Cellular bootlegging south of the soma

Neurons are responsible for the generation and propagation of electrical impulses, which constitute the central mechanism of information transfer between the nervous system and internal or external environments. Neurons are large and polarized cells with dendrites and axons constituting their major functional domains. Axons are thin and extremely long specializations that mediate the conduction of these electrical impulses. Regulation of the axonal proteome is fundamental to generate and maintain neural function. Although classical mechanisms of protein transport have been around for decades, a variety newly identified mechanisms to control the abundance of axonal proteins have appeared in recent years. Here we briefly describe the classical models of axonal transport and compare them to the emerging concepts of axonal biosynthesis centered on the endoplasmic reticulum. We review the structure of the axonal endoplasmic reticulum, and its role in diffusion and trafficking of axonal proteins. We also analyze the contribution of other secretory organelles to axonal trafficking and evaluate the potential consequences of axonal endoplasmic reticulum malfunction in neuropathology.