The role of EGF receptor ubiquitination in regulating its intracellular traffic.
Traffic. 2012 Feb; 13:329-37
Many receptors are modified by ubiquitination, which has been suggested to play a role in endocytosis. This paper shows that ubiquitination of epidermal growth factor receptor (EGFR) does not affect endocytosis per se but is critical for interaction with endosomal-sorting complex required for transport (ESCRT) component(s) and for EGFR-induced production of intraluminal vesicles (ILV) and the localization of EGFR to the ILV within multivesicular bodies (MVB) for down-regulation.
The authors comes to the conclusion that ubiquitination is required for EGFR entry to ILV by monitoring the behavior of an ubiquitination-defective EGFR mutant (15KR-EGFR) in the cell. In contrast to wild-type EGFR, 15KR-EGFR shows defects in the interaction with and phosphorylation of the Hrs component of the ESCRT complex. In addition, 15KR-EGFR is localized to the limiting membrane of MVB rather than ILV and is more efficiently recycled back to the cell surface, like the transferrin receptor.
This study shed light on the function of receptor ubiquitination in the biogenesis of MVB and cargo-mediated regulation of the endocytic pathway.
Please click here to access the full text of this article.
Li G: F1000Prime Recommendation of [Eden ER et al., Traffic 2012, 13:329-37]. In F1000Prime, 16 Dec 2011; DOI: 10.3410/f.13408022.14778136. F1000Prime.com/13408022#eval14778136
F1000Prime Recommendations, Dissents and Comments for [Eden ER et al., Traffic 2012, 13:329-37]. In F1000Prime, 05 Dec 2013; F1000Prime.com/13408022
Nat Cell Biol. 2004 Mar; 6(3):252-9
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.
© 2011 John Wiley & Sons A/S.
has been added to your "Faculty I'm Following" page in MyF1000
Follow/Unfollow any Faculty via their recommendations, biography pages, or MyF1000
If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password.
The email address should be the one you originally registered with F1000.
You registered with F1000 via Google, so we cannot reset your password.
To sign in, please click here.
If you still need help with your Google account password, please click here.
You registered with F1000 via Facebook, so we cannot reset your password.
To sign in, please click here.
If you still need help with your Facebook account password, please click here.
We have sent an email to , please follow the instructions to reset your password.
If you don't receive this email, please check your spam filters and/or contact email@example.com.