Year: 2019
Type: article
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.
Source: EMBO Reports
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,830
Awards: How changes in nutrient availability are sensed and shape metabolism and growth, Signalling mechanisms that determine the rate of ageing, G3074483764, G3124682028, To define the molecular mechanisms that determine cellular and organismal longevity, Characterisation of the PI3P-dependent signalling network responsible for nutrient sensing and autophagy, How autophagy and related processes are coordinated and important in adaption to changed nutrient availability and cell damage, To map the organisation of nutrient signalling pathways, G5058624343, G6371588837, G6580186668, G6640686762, G7255661211, G8869311580
OpenAlex ID: W2969219924