2024
Developmental Cell

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

Authors:

Max Koppers, Nazmiye Özkan, Ha H. Nguyen, Daphne Jurriens, Janine McCaughey, Dan T.M. Nguyen, Chun Hei Li, Riccardo Stucchi, Maarten Altelaar, Harold D. MacGillavry, Lukas C. Kapitein, Casper C. Hoogenraad, Ginny G. Farías

Keywords:

axonal protein synthesis; mRNA localization; endoplasmic reticulum; ribosomes; P180/RRBP1; ER-based translation; axonal ER; local translation; neuron development; ER shape

Abstract:

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.