title: A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium.
abstract: Members of the Rab guanosine triphosphatase (GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium). This mutant traffics to lysosomes and allowed us to determine which Rabs localize to a maturing phagosome. In total, 18 Rabs associated with maturing phagosomes, each with its own kinetics of association. Dominant-negative mutants of Rab23 and 35 inhibited phagosome-lysosome fusion. A large number of Rab GTPases localized to wild-type Salmonella-containing vacuoles (SCVs), which do not fuse with lysosomes. However, some Rabs (8B, 13, 23, 32, and 35) were excluded from wild-type SCVs whereas others (5A, 5B, 5C, 7A, 11A, and 11B) were enriched on this compartment. Our studies demonstrate that a complex network of Rab GTPases controls endocytic progression to lysosomes and that this is modulated by S. Typhimurium to allow its intracellular growth.
authors.affiliation: Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Smith
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.forename: Virginie
authors.initials: V
authors.lastname: Braun
authors.forename: Xiuju
authors.initials: X
authors.lastname: Jiang
authors.forename: Chloe
authors.initials: C
authors.lastname: Macrae
authors.forename: James E
authors.initials: JE
authors.lastname: Casanova
authors.forename: Marci A
authors.initials: MA
authors.lastname: Scidmore
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D009154:Mutation; D010588:Phagosomes / Q000201:enzymology*; D021381:Protein Transport / Q000502:physiology*; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics; D014617:Vacuoles / Q000201:enzymology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020691:rab GTP-Binding Proteins