Translating regeneration: Local protein synthesis in the neuronal injury response.

ABSTRACT

Neurons convey signals over long distances, for example motor neurons and sensory neurons project axons up to a meter long in humans. To this end, a sophisticated network of long-range signaling mechanisms enables communication between neuronal processes and somata. These mechanisms are activated during axonal injury and have essential roles both for sensing the injury and regulating subsequent regeneration. Here we survey the role of one such mechanism, axonal translation, which contributes to both retrograde injury signaling and as a source of proteins for regenerating axons. The nature of the axonal synthesis machinery has become progressively clearer over the past decade. A large number of axonally localized mRNAs have been identified, which cover a wide spectrum of protein families; and axonal ribosomes have been detected, even though their origin is still subject to debate. Various kinase pathways, most prominently mTOR, have been implicated in driving local translation in axons. Finally, new technologies are becoming available to visualize axonal translation and enable proteomic analyses. These technological improvements offer new avenues towards comprehensive characterization of the axonal translational machinery.