Targeting of Early Endosomes by Autophagy Facilitates EGFR Recycling and Signalling

Jane Fraser, Joanne Simpson, Rosa Fontana, Chieko Kishi-Itakura, Nicholas T Ktistakis, Noor Gammoh

Research output: Contribution to journalArticlepeer-review

Abstract

Despite recently uncovered connections between autophagy and the endocytic pathway, the role of autophagy in regulating endosomal function remains incompletely understood. Here, we find that the ablation of autophagy‐essential players disrupts EGF‐induced endocytic trafficking of EGFR. Cells lacking ATG7 or ATG16L1 exhibit increased levels of phosphatidylinositol‐3‐phosphate (PI(3)P), a key determinant of early endosome maturation. Increased PI(3)P levels are associated with an accumulation of EEA1‐positive endosomes where EGFR trafficking is stalled. Aberrant early endosomes are recognised by the autophagy machinery in a TBK1‐ and Gal8‐dependent manner and are delivered to LAMP2‐positive lysosomes. Preventing this homeostatic regulation of early endosomes by autophagy reduces EGFR recycling to the plasma membrane and compromises downstream signalling and cell survival. Our findings uncover a novel role for the autophagy machinery in maintaining early endosome function and growth factor sensing.
Original languageEnglish
Article numbere47734
Number of pages17
JournalEMBO Reports
Volume20
Issue number10
Early online date26 Aug 2019
DOIs
Publication statusPublished - 4 Oct 2019

Keywords

  • Autophagy
  • Early Endosomes
  • EGFR
  • Galectin
  • Signalling

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