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Clathrin-independent endocytosis of ubiquitinated cargos
Abstract
Plasma membrane receptors can be endocytosed through clathrin-dependent and clathrin-independent pathways. Here, we show that the epidermal growth factor (EGF) receptor (EGFR), when stimulated with low doses of EGF, is internalized almost exclusively through the clathrin pathway, and it is not ubiquitinated. At higher concentrations of ligand, however, a substantial fraction of the receptor is endocytosed through a clathrin-independent, lipid raft-dependent route, as the receptor becomes ubiquitinated. An ubiquitination-impaired EGFR mutant was internalized through the clathrin pathway, whereas an EGFR/ubiquitin chimera, that can signal solely through its ubiquitin (Ub) moiety, was internalized exclusively by the non-clathrin pathway. Non-clathrin internalization of ubiquitinated EGFR depends on its interaction with proteins harboring the Ub-interacting motif, as shown through the ablation of three Ub-interacting motif-containing proteins, eps15, eps15R, and epsin. Thus, eps15s and epsin perform an important function in coupling ubiquitinated cargo to clathrin-independent internalization.
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Postactivation endocytic trafficking of EGFR has been well elucidated.
“While postactivation endocytic trafficking of EGFR has been well elucidated, little is known about mechanisms of basal/preactivation surface display of EGFR.”
From EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling (2020) · cites this paper as [10]
Under low EGF (2.5 ng/ml), EGFR is expected to undergo canonical clathrin-mediated endocytosis with robust access to recycling and degradation.
“Under these conditions, EGFR is expected to undergo canonical clathrin-mediated endocytosis with robust access to recycling as well as degradation (42).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [42]
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Curvature of clathrin-coated pits driven by epsin
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Metadata
- Authors
- Sigismund, S., Woelk, T., Puri, C., Maspero, E., Tacchetti, C., Transidico, P., Di Fiore, P. P., & Polo, S.
- Affiliations
- Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-02-08
- Volume
- 102
- Issue
- 8
- Pages
- 2760-2765
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 739
- References
- 1
- Language
- en
- Update notices
- correction (2024-11-11)
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