Nature Neuroscience
- 9, 1247 - 1256 (2006)
Published online: 17 September 2006; | doi:10.1038/nn1775
Asymmetrical  -actin mRNA translation in growth cones mediates attractive turning to netrin-1Kin-Mei Leung1, 3, Francisca PG van Horck1, 3, Andrew C Lin1, Rachel Allison2, Nancy Standart2 & Christine E Holt11
Departments of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. 2
Departments of Biochemistry, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. 3
These authors contributed equally to this work.
Correspondence should be addressed to Christine E Holt ceh@mole.bio.cam.ac.uk 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  -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 -actin translation on the near side of the growth cone before growth cone turning. Inhibition of -actin translation abolishes both the asymmetric rise in -actin and attractive, but not repulsive, turning. Our data suggest that newly synthesized -actin, concentrated near sites of signal reception, provides the directional bias for polymerizing actin in the direction of an attractive stimulus.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
