title: Identification of an immune-regulated phagosomal Rab cascade in macrophages.
abstract: Interferon-γ (IFN-γ) has been shown to regulate phagosome trafficking and function in macrophages, but the molecular mechanisms involved are poorly understood. Here, we identify Rab20 as part of the machinery by which IFN-γ controls phagosome maturation. We found that IFN-γ stimulates the association of Rab20 with early phagosomes in macrophages. By using imaging of single phagosomes in live cells, we found that Rab20 induces an early delay in phagosome maturation and extends the time for which Rab5a and phosphatidylinositol 3-phosphate (PI3P) remain associated with phagosomes. Moreover, Rab20 depletion in macrophages abrogates the delay in phagosome maturation induced by IFN-γ. Finally, we demonstrate that Rab20 interacts with the Rab5a guanine nucleotide exchange factor Rabex-5 (also known as RABGEF1) and that Rab20 knockdown impairs the IFN-γ-dependent recruitment of Rabex-5 and Rab5a into phagosomes. Taken together, here, we uncover Rab20 as a key player in the Rab cascade by which IFN-γ induces a delay in phagosome maturation in macrophages.
authors.affiliation: Research Group Phagosome Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
authors.forename: Urska
authors.initials: U
authors.lastname: Repnik
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.forename: Maximiliano Gabriel
authors.initials: MG
authors.lastname: Gutierrez
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D019084:Fluorescent Antibody Technique, Indirect; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D018129:Phosphatidylinositol Phosphates; C108382:RABGEF1 protein, human; C055525:phosphatidylinositol 3-phosphate; C509832:Rab20 protein, human; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins
keywords: Lysosome; Macrophage; Phagosome; Rab; Rabex-5