RNA translation in axons

Abstract

The cell body has classically been considered the exclusive source of axonal proteins. However, significant evidence has accumulated recently to support the view that protein synthesis can occur in axons themselves, remote from the cell body. Indeed, local translation in axons may be integral to aspects of synaptogenesis, long-term facilitation, and memory storage in invertebrate axons, and for growth cone navigation in response to environmental stimuli in developing vertebrate axons. Here we review the evidence supporting mRNA translation in axons and discuss the potential roles that local protein synthesis may play during development and subsequent neuronal function. We advance the view that local translation provides a rapid supply of nascent proteins in restricted axonal compartments that can potentially underlie long-term responses to transient stimuli.

Figure 1

Regenerating sensory axons require local protein synthesis (yellow) to maintain growth cone advancement. Model based on Zheng et al. (2001).

Figure 2

Intracellular pathways leading to initiation of RNA translation in the growth cone. Sema3A and netrin-1 signal through different mitogen-activated protein kinase (MAPK) molecules that converge on mTOR and lead to an increase in phosphorylation of translation initiation factors and local protein synthesis, which subsequently mediates growth cone steering responses to these guidance cues (adapted from Campbell & Holt 2003).

Figure 3

Diagram illustrating hypothesized roles of axonal protein synthesis in developing axons. (a) Growth cones approach a directional cue (blue) such as Sema3A at an angle (1); filopodia on the cue-side of the growth cone are stimulated first and translation (purple spots) is elicited asymmetrically (2), leading to local collapse on the cue-side and subsequent repulsive turning (3). Model based on Campbell & Holt (2001). (b) Growth cones approach (1) and extend through (2) an intermediate target (green) expressing a cue that elicits the translation of RNAs encoding new proteins (red) needed for responding to a second cue (blue) encountered later in the journey (3). Model based on Brittis et al. (2002).