A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium.
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.
Smith
Adam C
AC
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8.
Heo
Won Do
WD
Braun
Virginie
V
Jiang
Xiuju
X
Macrae
Chloe
C
Casanova
James E
JE
Scidmore
Marci A
MA
Grinstein
Sergio
S
Meyer
Tobias
T
Brumell
John H
JH
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*
D020691:rab GTP-Binding Proteins