Nature Neuroscience
- 9, 1265 - 1273 (2006)
Published online: 17 September 2006; | doi:10.1038/nn1773
An essential role for  -actin mRNA localization and translation in Ca2+-dependent growth cone guidanceJiaqi Yao1, Yukio Sasaki2, Zhexing Wen1, Gary J Bassell2 & James Q Zheng11
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA. 2
Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA.
Correspondence should be addressed to James Q Zheng zhengjq@umdnj.edu Axon pathfinding requires directional responses of growth cones to extracellular cues, which have been shown to involve local synthesis of protein. The identity and functions of the locally produced proteins remain, however, unclear. Here we report that Ca2+-dependent bidirectional turning of Xenopus laevis growth cones requires localized distribution and translation of  -actin messenger RNA. Both -actin mRNA and its zipcode-binding protein, ZBP1, are localized at the growth cone and become asymmetrically distributed upon local exposure to brain-derived neurotrophic factor (BDNF). Inhibition of protein synthesis or antisense interference with -actin mRNA–ZBP1 binding abolishes both Ca2+-mediated attraction and repulsion. In addition, attraction involves a local increase in -actin, whereas repulsion is accompanied by a local decrease in -actin; thus, both produce a synthesis- and ZBP1 binding–dependent -actin asymmetry but with opposite polarities. Together with a similar asymmetry in Src activity during bidirectional responses, our findings indicate that Ca2+-dependent spatial regulation of -actin synthesis through Src contributes to the directional motility of growth cones during guidance.
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