Clathrin-independent endocytosis of ubiquitinated cargos

• DOI: 10.1073/pnas.0409817102
• Publication Date: 2005-02-09T04:03:45Z
• Authors: Sara Sigismund; Tanja Woelk; Claudia Puri; Elena Maspero; Carlo Tacchetti; Pietro Transidico; Pier Paolo Di Fiore; Simona Polo
• Keywords: Internalization; Lipid raft

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 clathrin pathway, it not ubiquitinated. At higher concentrations ligand, however, a substantial fraction clathrin-independent, lipid raft-dependent route, as becomes An ubiquitination-impaired EGFR mutant was whereas an EGFR/ubiquitin chimera, signal solely its ubiquitin (Ub) moiety, by non-clathrin pathway. Non-clathrin internalization ubiquitinated depends on interaction proteins harboring Ub-interacting motif, shown ablation three motif-containing proteins, eps15, eps15R, epsin. Thus, eps15s epsin perform important function in coupling cargo to internalization.