The role of EGF receptor ubiquitination in regulating its intracellular traffic.
Progression of activated EGF receptor (EGFR) through the endocytic pathway regulates EGFR signaling. Here we show that a non-ubiquitinated EGFR mutant, unable to bind the endosomal-sorting complex required for transport (ESCRT) component, Hrs, is not efficiently targeted onto intraluminal vesicles (ILVs) of multivesicular endosomes/bodies (MVBs). Moreover, ubiquitination and ESCRT engagement of activated EGFR are required for EGF-stimulated ILV formation. Non-ubiquitinated EGFRs enter clathrin-coated tubules emanating from MVBs and show enhanced recycling to the plasma membrane, compared to wild-type EGFR.
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Emily R
ER
Eden
Fangtian
F
Huang
Alexander
A
Sorkin
Clare E
CE
Futter
D000818:Animals; D001011:Aorta / Q000166:cytology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D057146:Multivesicular Bodies / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D034421:Sus scrofa; D014162:Transfection; D014168:Transferrin / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
D002966:Clathrin; D056827:Endosomal Sorting Complexes Required for Transport; D021122:Protein Subunits; D014168:Transferrin; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3