Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.
Holtermann, Anne V
Harris, William A
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Cioni, J., Lin, Q., Holtermann, A. V., Koppers, M., Jakobs, M., Azizi, A., Turner-Bridger, B., et al. (2019). Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.. Cell, 176 (1-2), 56-72.e15. https://doi.org/10.1016/j.cell.2018.11.030
Local translation regulates the axonal proteome, playing an important role in neuronal wiring and axon maintenance. How axonal mRNAs are localized to specific subcellular sites for translation, however, is not understood. Here, we report that RNA granules associate with endosomes along the axons of retinal ganglion cells. RNA-bearing Rab7a-late endosomes also associate with ribosomes, and real-time translation imaging reveals that they are sites of local protein synthesis. We show that RNA-bearing late endosomes often pause on mitochondria and that mRNAs encoding proteins for mitochondrial function are translated on Rab7a-endosomes. Disruption of Rab7a function with Rab7a mutants, including those associated with Charcot-Marie-Tooth type 2B neuropathy, markedly decreases axonal protein synthesis, impairs mitochondrial function and compromises axonal viability. Our findings thus reveal that late endosomes interact with RNA granules, translation machinery and mitochondria, and suggest that they serve as sites for regulating the supply of nascent pro-survival proteins in axons.
Axons, Retinal Ganglion Cells, Endosomes, Mitochondria, Ribosomes, Animals, Xenopus laevis, rab GTP-Binding Proteins, Xenopus Proteins, RNA, RNA, Messenger, Protein Biosynthesis
Wellcome Trust (085314/Z/08/Z)
European Research Council (322817)
Wellcome Trust (203249/Z/16/Z)
Wellcome Trust (100329/Z/12/Z)
External DOI: https://doi.org/10.1016/j.cell.2018.11.030
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287127