title: Interferon-γ-inducible Rab20 regulates endosomal morphology and EGFR degradation in macrophages.
abstract: Little is known about the molecular players that regulate changes in the endocytic pathway during immune activation. Here we investigate the role of Rab20 in the endocytic pathway during activation of macrophages. Rab20 is associated with endocytic structures, but the function of this Rab GTPase in the endocytic pathway remains poorly characterized. We find that in macrophages, Rab20 expression and endosomal association significantly increase after interferon-γ (IFN-γ) treatment. Moreover, IFN-γ and Rab20 expression induce a dramatic enlargement of endosomes. These enlarged endosomes are the result of homotypic fusion promoted by Rab20 expression. The expression of Rab20 or the dominant-negative mutant Rab20T19N does not affect transferrin or dextran 70 kDa uptake. However, knockdown of Rab20 accelerates epidermal growth factor (EGF) trafficking to LAMP-2-positive compartments and EGF receptor degradation. Thus this work defines a function for Rab20 in the endocytic pathway during immune activation of macrophages.
authors.affiliation: Research Group Phagosome Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Schnettger
authors.affiliation: Research Group Phagosome Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Bronietzki
authors.affiliation: Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
authors.forename: Urska
authors.initials: U
authors.lastname: Repnik
authors.affiliation: Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, United Kingdom Maximiliano.Gutierrrez@crick.ac.uk.
authors.forename: Maximiliano Gabriel
authors.initials: MG
authors.lastname: Gutierrez
mesh_terms: D000818:Animals; D003911:Dextrans / Q000494:pharmacology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D000067996:RAW 264.7 Cells; D014168:Transferrin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D003911:Dextrans; D014168:Transferrin; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; C541485:EGFR protein, mouse; D066246:ErbB Receptors; C092933:Rab20 protein, mouse; D020691:rab GTP-Binding Proteins