title: Rab7 is functionally required for selective cargo sorting at the early endosome.
abstract: The small GTPases of the Rab family act as a molecular switch regulating various aspects of membrane trafficking through the selective recruitment of effector proteins. Whereas Rab7 has been classically involved in the regulation of transport within the endolysosomal network, persistent controversy remains as to whether Rab7 also plays a role in earlier steps of endosomal trafficking. In this study, we show that Rab7 depletion or inactivation results in enlargement of both early and late endosomes. Rab7 depletion led to the retention of a significant fraction of internalized low-density lipoproteins (LDL) mainly in enlarged early endosomes (EE). As a result, LDL processing and the transcriptional regulation of sterol-sensitive genes were impaired. We found that Rab7 activity was also required for the sorting of the mannose-6-phosphate receptor, the interferon alpha-receptor and the Shiga toxin B-subunit. In contrast, epidermal growth factor (EGF) sorting at the EE or the recycling of transferrin and LDL-R were not affected by Rab7 depletion. Our findings demonstrate that in addition to regulating late endosomes (LE) to lysosomes transport, Rab7 plays a functional role in the selective sorting of distinct cargos at the EE and that the Rab5 to Rab7 exchange occurs early in the endosomal maturation process.
authors: AP-HP (Assistance Publique - Hôpitaux de Paris), Hôpital Européen Georges Pompidou, Service de Biochimie, 75015, Paris, France; Université Paris-Sud, EA 4529, UFR de Pharmacie, 92296, Châtenay-Malabry, France; CNRS UMR144, 75248 Paris cedex 05, France; Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, 75248, Paris Cedex 05, France.
authors: Emmanuelle
authors: E
authors: Girard
authors: Daniela
authors: D
authors: Chmiest
authors: Natalie
authors: N
authors: Fournier
authors: Ludger
authors: L
authors: Johannes
authors: Jean-Louis
authors: JL
authors: Paul
authors: Benoît
authors: B
authors: Vedie
authors: Christophe
authors: C
authors: Lamaze
mesh_terms: D002784:Cholesterol / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D022641:Shiga Toxin 2 / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D017527:Receptor, IGF Type 2; D022641:Shiga Toxin 2; D014168:Transferrin; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C450841:shiga toxin 2 B subunit; D053633:Receptor, Interferon alpha-beta; D004815:Epidermal Growth Factor; D002784:Cholesterol; D020691:rab GTP-Binding Proteins
keywords: Rab7; cholesterol; endocytosis; endosome; trafficking