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Nat Neurosci. 2006 Oct;9(10):1247-56. Epub 2006 Sep 17.

Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1.

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1
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

Abstract

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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PMID:
16980963
PMCID:
PMC1997306
DOI:
10.1038/nn1775
[Indexed for MEDLINE]
Free PMC Article

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