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Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling
Author(s) -
Fraser Jane,
Simpson Joanne,
Fontana Rosa,
KishiItakura Chieko,
Ktistakis Nicholas T,
Gammoh Noor
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201947734
Subject(s) - endosome , autophagy , endocytic cycle , microbiology and biotechnology , biology , lysosome , endocytosis , cell , biochemistry , intracellular , apoptosis , enzyme
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 ATG 7 or ATG 16L1 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 EEA 1‐positive endosomes where EGFR trafficking is stalled. Aberrant early endosomes are recognised by the autophagy machinery in a TBK 1‐ and Gal8‐dependent manner and are delivered to LAMP 2‐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.