Journal
EMBO REPORTS
Volume 20, Issue 10, Pages -Publisher
WILEY
DOI: 10.15252/embr.201947734
Keywords
autophagy; early endosomes; EGFR; galectin; signalling
Categories
Funding
- Cancer Research UK fellowship [C52370/A21586]
- BBSRC [BBS/E/B/000C0433, BBS/E/B/000C0413, BBS/E/B/000C0417, BB/H000631/1, BBS/E/B/000C0432, BBS/E/B/000C0434] Funding Source: UKRI
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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.
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