Function and translational regulation of mRNA in developing axons

Abstract

The capacity to synthesize proteins in axons is limited to early stages of neuronal development, while axons are undergoing elongation and pathfinding. Although the roles of local protein synthesis are not fully understood, it has been implicated in regulating the morphological plasticity of growth cones. Recent studies have identified specific mRNAs that are translated in growth cones in response to specific extracellular signals. In this review, we discuss the functional relevance of axonal protein translation for developing axons, the differences in translational capacity between developing and mature vertebrate axons, and possible pathways governing the specific translational activation of axonal mRNAs.

Figure 1

dEGFP puncta indicating sites of local translation (green) co-localize (yellow) with a subpopulation ribosomal protein S6-positive clusters (red).

Figure 2

Schematic of proposed signaling pathways regulating mRNA translation in growth cones. Conceivably, axonal mRNAs may be localized to P bodies, sites of microRNA-mediated mRNA translation suppression, and released from these sites upon exposure to translation-inducing stimuli. Axonal mRNAs may also be repressed by phosphorylated FMRP, which may mediate its translational inhibition by recruitment of RISC proteins or microRNAs. Dephosphorylation of FMRP alleviates the inhibition of stalled ribosomes, thereby leading to enhanced local translation.