Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1.
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.
Leung
Kin-Mei
KM
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
van Horck
Francisca P G
FP
Lin
Andrew C
AC
Allison
Rachel
R
Standart
Nancy
N
Holt
Christine E
CE
D020413:3' Untranslated Regions / Q000008:administration & dosage; D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008845:Microinjections / Q000379:methods; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D014176:Protein Biosynthesis / Q000502:physiology*; D011554:Pseudopodia / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000494:pharmacology; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis
D020413:3' Untranslated Regions; D000199:Actins; D004268:DNA-Binding Proteins; C498635:IGF2BP3 protein, Xenopus; D009414:Nerve Growth Factors; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins; D000075388:Netrin-1