Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons
| Autor: | Cioni, Jean-Michel, Lin, Julie Qiaojin, Holtermann, Anne V, Koppers, Max, Jakobs, Maximilian AH, Azizi, Afnan, Turner-Bridger, Benita, Shigeoka, Toshiaki, Franze, Kristian, Harris, William A, Holt, Christine E |
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| Přispěvatelé: | Lin, Qiaojin [0000-0002-2669-6478], Koppers, Max [0000-0002-7751-1082], Jakobs, Maximilian [0000-0002-0879-7937], Azizi, Afnan [0000-0002-3288-9612], Turner-Bridger, Benita [0000-0003-3718-3632], Franze, Kristian [0000-0002-8425-7297], Harris, William [0000-0002-9995-8096], Holt, Christine [0000-0003-2829-121X], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
Charcot-Marie-Tooth type 2B
Retinal Ganglion Cells mRNA translation rab7 GTP-Binding Proteins Endosomes Xenopus Proteins Article Axons Mitochondria Xenopus laevis nervous system rab GTP-Binding Proteins Protein Biosynthesis lysosome Animals RNA local protein synthesis RNA Messenger retinal ganglion cell axon maintenance endosome Ribosomes RNA trafficking |
| Zdroj: | Cell |
| DOI: | 10.17863/cam.34436 |
| Popis: | Summary 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. Graphical Abstract Highlights • Ribonucleoprotein particles are associated with endosomes in axons • Rab7a endosomes provide sites for axonal local translation • Rab7a endosomes support axonal synthesis of survival factors • CMT2B-Rab7a mutations affect axonal translation and mitochondrial integrity Late endosomes are sites of local translation of mRNAs important for mitochondrial maintenance, and perturbing this process can contribute to neuropathology, as seen in Charcot Marie-Tooth disease. |
| Databáze: | OpenAIRE |
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