Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.
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Authors
Cioni, Jean-Michel
Lin, Julie Qiaojin
Holtermann, Anne V
Jakobs, Maximilian AH
Shigeoka, Toshiaki
Harris, William A
Holt, Christine E
Publication Date
2019-01-10Journal Title
Cell
ISSN
0092-8674
Publisher
Elsevier BV
Volume
176
Issue
1-2
Pages
56-72.e15
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Cioni, J., Lin, J. Q., Holtermann, A. V., Koppers, M., Jakobs, M. A., 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
Abstract
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.
Keywords
Charcot-Marie-Tooth type 2B, RNA trafficking, axon maintenance, endosome, local protein synthesis, lysosome, mRNA translation, mitochondria, retinal ganglion cell, Animals, Axons, Endosomes, Mitochondria, Protein Biosynthesis, RNA, RNA, Messenger, Retinal Ganglion Cells, Ribosomes, Xenopus Proteins, Xenopus laevis, rab GTP-Binding Proteins, rab7 GTP-Binding Proteins
Sponsorship
Wellcome Trust (085314/Z/08/Z)
European Research Council (322817)
Wellcome Trust (203249/Z/16/Z)
Wellcome Trust (100329/Z/12/Z)
Biotechnology and Biological Sciences Research Council (BB/N006402/1)
Identifiers
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
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http://www.rioxx.net/licenses/all-rights-reserved
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