Axonal ER tubules control local translation via P180/RRBP1-mediated ribosome interactions

Local mRNA translation in axons is critical for the spatial and temporal 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 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 an important role for the axonal ER in dynamically localizing mRNA translation which is important for proper neuron development.轴突内的局部mRNA翻译对于轴突蛋白质组的时空调控至关重要。多种mRNA可在轴突中定位并完成翻译，但目前尚不明确蛋白质合成如何在轴突的特定亚细胞位点受到调控。本研究证实，轴突内质网（axonal endoplasmic reticulum, ER）可支持发育神经元中的轴突翻译过程。轴突内质网管状结构的破坏会损害局部翻译及核糖体的分布。借助纳米分辨率成像技术，我们发现核糖体以翻译依赖的方式频繁与轴突内质网管状结构发生接触，且该过程受特定外在信号的调控。我们鉴定出P180/RRBP1作为一种轴突分布的核糖体受体，其可调控局部翻译并结合富含轴突膜蛋白编码序列的mRNA。值得注意的是，轴突内质网与核糖体相互作用的受损会导致轴突形态出现异常。本研究结果证实，轴突内质网在动态调控mRNA翻译的定位过程中发挥重要作用，这对于神经元的正常发育具有关键意义。