title: The ERM proteins interact with the HOPS complex to regulate the maturation of endosomes.
abstract: In the degradative pathway, the progression of cargos through endosomal compartments involves a series of fusion and maturation events. The HOPS (homotypic fusion and protein sorting) complex is part of the machinery that promotes the progression from early to late endosomes and lysosomes by regulating the exchange of small GTPases. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation. This impairment in EGFR trafficking observed in cells depleted of ERM proteins is due to a delay in the recruitment of Rab7 on endosomes. As a consequence, the maturation of endosomes is perturbed as reflected by an accumulation of hybrid compartments positive for both early and late endosomal markers. Thus, ERM proteins represent novel regulators of the HOPS complex in the early to late endosomal maturation.
authors.affiliation: Institut Curie-Unité Mixte de Recherche 144 (UMR144), Centre National de la Recherche Scientifique (CNRS)/Morphogenèse et Signalisation cellulaires, Paris, France.
authors.forename: Dafne
authors.initials: D
authors.lastname: Chirivino
authors.forename: Laurence
authors.initials: L
authors.lastname: Del Maestro
authors.forename: Etienne
authors.initials: E
authors.lastname: Formstecher
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Daniel
authors.initials: D
authors.lastname: Louvard
authors.forename: Monique
authors.initials: M
authors.lastname: Arpin
mesh_terms: D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D066246:ErbB Receptors; D008565:Membrane Proteins; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; D000099149:Ezrin; C424438:VPS11 protein, human; C000716463:rab7 GTP-binding proteins, human; C071058:moesin; C071776:radixin