Intra-axonal protein synthesis in development and beyond

Abstract

Proteins can be locally produced in the periphery of a cell, allowing a rapid and spatially precise response to the changes in its environment. This process is especially relevant in highly polarized and morphologically complex cells such as neurons. The study of local translation in axons has evolved from being primarily focused on developing axons, to the notion that also mature axons can produce proteins. Axonal translation has been implied in several physiological and pathological conditions, and in all cases it shares common molecular actors and pathways as well as regulatory mechanisms. Here, we review the main findings in these fields, and attempt to highlight shared principles.

Keywords: Axon growth/branching; Axonal translation; Nerve injury; Neurodegeneration; Synapse formation; mRNA.

Figure

In developing axons, local protein synthesis of cytoskeletal regulators supports: axons branching in response to growth factors (brown), axonal elongation and attractive turning triggered by attractive guidance cues (green), and growth cone collapse and axonal retraction induced by repulsive guidance cues (magenta). Local growth factor signalling triggers intra-axonal synthesis of transcription factors that are required for cell survival or specification (yellow). In mature neurons, local protein synthesis supports axon maintenance through the local synthesis of mitochondria-associated proteins (brown). Neurodegenerative insults and nerve injury activate local protein synthesis of transcription factors that can cause cell death or initiate a regenerative response, respectively (green, yellow). Local synthesis of in presynaptic terminals is involved in synapse formation but its role in synapse function or maintenance remains unknown (magenta).