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Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.

Cell | 2019

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.

Pubmed ID: 30612743 RIS Download

Research resources used in this publication

Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 203249/Z/16/Z
  • Agency: European Research Council, International
    Id: 322817
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/N006402/1
  • Agency: Wellcome Trust, United Kingdom
    Id: 100329/Z/12/Z
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/N006402/1
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 085314/Z/08/Z

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This is a list of tools and resources that we have found mentioned in this publication.


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RRID:XEP_Xla100

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RRID:SCR_002668

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RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

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RRID:AB_945424

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Anti-Puromycin Antibody, clone 12D10 (antibody)

RRID:AB_2566826

This monoclonal targets Puromycin from Streptomyces alboniger

View all literature mentions

Phospho-S6 Ribosomal Protein (Ser235/236) Antibody (antibody)

RRID:AB_331679

This polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)

View all literature mentions

mTOR (7C10) Rabbit mAb (antibody)

RRID:AB_2105622

This monoclonal targets mTOR

View all literature mentions

Recombinant Anti-mTOR (phospho S2448) antibody [EPR426(2)] (antibody)

RRID:AB_10888105

This recombinant monoclonal targets mTOR (phospho S2448)

View all literature mentions

Phospho-Akt (Ser473) Antibody (antibody)

RRID:AB_329825

This polyclonal targets Phospho-Akt (Ser473)

View all literature mentions

RPL10A antibody (antibody)

RRID:AB_2181281

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RPL24 antibody (antibody)

RRID:AB_2181728

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