Potential functional roles of localized RNAs, discussed in the text. Localized RNAs can be translated into proteins that (a) are targeted to specific membrane compartments, (b) carry post-translational modifications (*) distinct from those carried by pre-existing protein or protein found at other cellular locations, (c) form specific complexes with other binding-partners or (d) are trafficked to other locations to mediate communication between cellular compartments. Localized RNAs can also exert translation-independent roles, such as participating as structural components of ribonucleoprotein complexes (e).

A. ZBP1- and APC-mediated RNA localization pathways in a migrating cell. See text for details. B. Association of APC with distinct cellular complexes. APC participates, together with β-catenin, axin and GSK3β, in the ‘destruction complex’. In the absence of Wnt signaling (left panel), β-catenin is phosphorylated and targeted for degradation by the 26S proteasome. An apparently separate pool of APC is found at the plus ends of Glu-MTs in association with several mRNAs. Upon Wnt signaling activation (right panel), inactivation of GSK3β leads to stabilization of β-catenin, which enters the nucleus and activates transcription of Wnt-target genes. Stabilized β-catenin can also directly block APC function at MT-ends.

Schematic depicting the proposed role for localized RNAs in establishing new directions of polarity during growth cone turning. A positive feedback loop between components A and B maintains a stable axis of polarity so that outgrowth persists towards a specific direction (maintenance of polarity also likely requires the action of lateral inhibitors, which are not depicted here for simplicity). In response to a guidance cue, dynamic MTs transport β-actin mRNA and likely other localized RNPs. Additionally, a local increase in Src kinase activity relieves the translational repression of β-actin mRNA mediated by ZBP1. This leads to a local increase in the amount of β-actin (and likely of other proteins produced by localized RNAs). We hypothesize that this local increase in concentrations and activities plays an important role in re-orienting the polarity axis towards a new direction. Other proteins translated from (or affected by) such localized RNAs could correspond to factors A or B or to regulators of them.