Journal
NATURE NEUROSCIENCE
Volume 9, Issue 10, Pages 1247-1256Publisher
NATURE RESEARCH
DOI: 10.1038/nn1775
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Funding
- Biotechnology and Biological Sciences Research Council [BB/C514766/1] Funding Source: Medline
- Wellcome Trust [070568] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BB/C514766/1] Funding Source: researchfish
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Local protein synthesis regulates the turning of growth cones to guidance cues, yet little is known about which proteins are synthesized or how they contribute to directional steering. Here we show that beta-actin mRNA resides in Xenopus laevis retinal growth cones where it binds to the RNA-binding protein Vg1RBP. Netrin-1 induces the movement of Vg1RBP granules into filopodia, suggesting that it may direct the localization and translation of mRNAs in growth cones. Indeed, a gradient of netrin-1 activates a translation initiation regulator, eIF-4E-binding protein 1 (4EBP), asymmetrically and triggers a polarized increase in beta-actin translation on the near side of the growth cone before growth cone turning. Inhibition of beta-actin translation abolishes both the asymmetric rise in beta-actin and attractive, but not repulsive, turning. Our data suggest that newly synthesized beta-actin, concentrated near sites of signal reception, provides the directional bias for polymerizing actin in the direction of an attractive stimulus.
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