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Published online
doi:10.1083/jcb.200611056
The Journal of Cell Biology, Vol. 176, No. 3, 263-268
The Rockefeller University Press, 0021-9525 $30.00
© Smith et al.
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A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium



Adam C. Smith1,2, Won Do Heo4, Virginie Braun1, Xiuju Jiang1, Chloe Macrae3,5, James E. Casanova6, Marci A. Scidmore7, Sergio Grinstein1, Tobias Meyer4, and John H. Brumell1,2

1 Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8
2 Department of Medical Genetics and Microbiology and 3 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, M5S 1A8
4 Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305
5 Ontario Cancer Institute, Toronto, Ontario, Canada, M5G 2M9
6 Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908
7 Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

Correspondence to John Brumell: john.brumell{at}sickkids.ca

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.

Abbreviations used in this paper: DN, dominant-negative; Inv, invasin; LAMP-1, lysosomal-associated membrane protein-1; NPC1, Niemann-Pick C1; p.i., post infection; SCV, Salmonella-containing vacuole; Sif, Salmonella-induced filament; SPI, Salmonella pathogenicity island; S. Typhimurium, Salmonella enterica serovar Typhimurium; TTSS, type III secretion system.


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