Hengst Ulrich, Deglincerti Alessia, Kim Hyung Joon, Jeon Noo Li, Jaffrey Samie R
Department of Pharmacology, Weill Medical College, Cornell University, NY 10065, USA.
Nat Cell Biol. 2009 Aug;11(8):1024-30. doi: 10.1038/ncb1916. Epub 2009 Jul 20.
During development, axon growth rates are precisely regulated to provide temporal control over pathfinding. The precise temporal regulation of axonal growth is a key step in the formation of functional synapses and the proper patterning of the nervous system. The rate of axonal elongation is increased by factors such as netrin-1 and nerve growth factor (NGF), which stimulate axon outgrowth using incompletely defined pathways. To clarify the mechanism of netrin-1- and NGF-stimulated axon growth, we explored the role of local protein translation. We found that intra-axonal protein translation is required for stimulated, but not basal, axon outgrowth. To identify the mechanism of translation-dependent outgrowth, we examined the PAR complex, a cytoskeleton regulator. We found that the PAR complex, like local translation, is required for stimulated, but not basal, outgrowth. Par3 mRNA is localized to developing axons, and NGF and netrin-1 trigger its local translation. Selective ablation of Par3 mRNA from axons abolishes the outgrowth-promoting effect of NGF. These results identify a new role for local translation and the PAR complex in axonal outgrowth.
在发育过程中，轴突生长速率受到精确调控，以实现对路径寻找的时间控制。轴突生长的精确时间调控是功能性突触形成和神经系统正确模式化的关键步骤。轴突伸长速率会因诸如网蛋白-1和神经生长因子（NGF）等因素而增加，这些因素通过不完全明确的途径刺激轴突生长。为阐明网蛋白-1和NGF刺激轴突生长的机制，我们探究了局部蛋白质翻译的作用。我们发现，轴突内蛋白质翻译对于受刺激而非基础的轴突生长是必需的。为确定翻译依赖性生长的机制，我们研究了PAR复合体，一种细胞骨架调节因子。我们发现，PAR复合体与局部翻译一样，对于受刺激而非基础的生长是必需的。Par3 mRNA定位于发育中的轴突，NGF和网蛋白-1触发其局部翻译。从轴突中选择性去除Par3 mRNA会消除NGF的促生长作用。这些结果确定了局部翻译和PAR复合体在轴突生长中的新作用。
