Local mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.

轴突中的局部 mRNA 翻译对于轴突蛋白质组的时空调控至关重要。多种 mRNA 在轴突中定位和翻译;然而，轴突中特定亚细胞位点的蛋白质合成如何调节仍不清楚。在这里，我们确定轴突内质网 （ER） 支持发育中的大鼠海马培养神经元的轴突翻译。轴突 ER 小管破坏损害局部翻译和核糖体分布。使用纳米级分辨率成像，我们发现核糖体以翻译依赖性方式与轴突 ER 小管频繁接触，并受到特定外源性线索的影响。我们确定 P180/RRBP1 是一种轴突分布的核糖体受体，可调节局部翻译并与富含轴突膜蛋白的 mRNA 结合。重要的是，轴突 ER-核糖体相互作用的损伤会导致轴突形态缺陷。我们的结果确定了轴突 ER 在动态定位 mRNA 翻译中的作用，这对于神经元的正常发育很重要。