RNA-binding proteins and translational regulation in axons and growth cones

Abstract

RNA localization and regulation play an important role in the developing and adult nervous system. In navigating axons, extrinsic cues can elicit rapid local protein synthesis that mediates directional or morphological responses. The mRNA repertoire in axons is large and dynamically changing, yet studies suggest that only a subset of these mRNAs are translated after cue stimulation, suggesting the need for a high level of translational regulation. Here, we review the role of RNA-binding proteins (RBPs) as local regulators of translation in developing axons. We focus on their role in growth, guidance, and synapse formation, and discuss the mechanisms by which they regulate translation in axons.

Keywords: RNA-binding proteins; axon guidance; axon outgrowth; local translation; synapse formation.

Figure 1

Diagram summarizing RBP-mediated regulation of different cue-stimulated responses in axonal growth cones. In the growth cone, RBPs mediate translation of specific mRNAs after cue stimulation. Netrin-1 induces ZBP1 localization and translation of β-actin close to the source of Netrin-1, and this is crucial for growth cone turning (Leung et al., ; Lin and Holt, 2007). BDNF induces Src-mediated ZBP1 phosphorylation, β-actin translation and growth cone turning toward the BDNF source (Yao et al., ; Sasaki et al., 2010). Growth cone collapses and Map1B mRNA translation in response to Sema3a is attenuated in axons depleted of FMRP, suggesting a role for FMRP in Sema3A-mediated axon guidance (Li et al., 2009). NT3 induces CamKII mediated phosphorylation of CPEB1, which activates polyadenylation and translation of β-catenin mRNA crucial for axon elongation and branching (Kundel et al., 2009).