Yao Jiaqi, Sasaki Yukio, Wen Zhexing, Bassell Gary J, Zheng James Q
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.
Nat Neurosci. 2006 Oct;9(10):1265-73. doi: 10.1038/nn1773. Epub 2006 Sep 17.
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 Ca(2+)-dependent bidirectional turning of Xenopus laevis growth cones requires localized distribution and translation of beta-actin messenger RNA. Both beta-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 beta-actin mRNA-ZBP1 binding abolishes both Ca(2+)-mediated attraction and repulsion. In addition, attraction involves a local increase in beta-actin, whereas repulsion is accompanied by a local decrease in beta-actin; thus, both produce a synthesis- and ZBP1 binding-dependent beta-actin asymmetry but with opposite polarities. Together with a similar asymmetry in Src activity during bidirectional responses, our findings indicate that Ca(2+)-dependent spatial regulation of beta-actin synthesis through Src contributes to the directional motility of growth cones during guidance.
轴突寻路需要生长锥对细胞外信号做出定向反应，研究表明这涉及蛋白质的局部合成。然而，局部产生的蛋白质的身份和功能仍不清楚。在此，我们报告非洲爪蟾生长锥的钙依赖双向转向需要β-肌动蛋白信使核糖核酸的局部分布和翻译。β-肌动蛋白信使核糖核酸及其邮政编码结合蛋白ZBP1都定位于生长锥，并在局部暴露于脑源性神经营养因子（BDNF）时变得不对称分布。抑制蛋白质合成或对β-肌动蛋白信使核糖核酸-ZBP1结合进行反义干扰会消除钙介导的吸引和排斥。此外，吸引涉及β-肌动蛋白的局部增加，而排斥则伴随着β-肌动蛋白的局部减少；因此，两者都产生了依赖于合成和ZBP1结合的β-肌动蛋白不对称性，但极性相反。与双向反应期间Src活性的类似不对称性一起，我们的研究结果表明，通过Src对β-肌动蛋白合成进行钙依赖的空间调节有助于生长锥在导向过程中的定向运动。
