Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling

  • Fraser J
  • Simpson J
  • Fontana R
  • et al.
62Citations
Citations of this article
81Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

© 2019 The Authors. Published under the terms of the CC BY 4.0 license 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.

Cite

CITATION STYLE

APA

Fraser, J., Simpson, J., Fontana, R., Kishi‐Itakura, C., Ktistakis, N. T., & Gammoh, N. (2019). Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling. EMBO Reports, 20(10). https://doi.org/10.15252/embr.201947734

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free