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

Cell. 2019 Jan 10;176(1-2):56-72.e15. doi: 10.1016/j.cell.2018.11.030. Epub 2019 Jan 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Endosomes / metabolism
  • Endosomes / physiology*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Protein Biosynthesis / physiology*
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • RNA, Messenger / physiology
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / physiology
  • Ribosomes / metabolism
  • Xenopus Proteins / metabolism
  • Xenopus laevis / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab GTP-Binding Proteins / physiology

Substances

  • RNA, Messenger
  • Xenopus Proteins
  • rab7 protein
  • RNA
  • rab GTP-Binding Proteins