Nature Cell Biology
- 8, 971 - 977 (2006)
Published online: 13 August 2006; | doi:10.1038/ncb1463
The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factorTakahiro Murata1, 4, Anna Delprato2, Alyssa Ingmundson1, Derek K. Toomre3, David G. Lambright2 & Craig R. Roy11
Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA. 2
Department of Molecular Medicine, UMASS Medical School Two Biotech, 373 Plantation Street, Worcester, MA 01605, USA. 3
Department of Cell Biology, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA. 4
Current address: Department of Pediatrics, Mizonokuchi Hospital, Teikyo University School of Medicine, 3-8-3 Mizonokuchi, Takatsuku, Kawasaki 213-8507, Japan.
Correspondence should be addressed to Craig R. Roy craig.roy@yale.edu RalFCyaLidAdotARab5Rab7Rab2Rab6Rab18Rab35The intracellular pathogen Legionella pneumophila avoids fusion with lysosomes and subverts membrane transport from the endoplasmic reticulum to create an organelle that supports bacterial replication1,
2. Transport of endoplasmic reticulum-derived vesicles to the Legionella-containing vacuole (LCV) requires bacterial proteins that are translocated into host cells by a type IV secretion apparatus called Dot/Icm3,
4,
5,
6,
7. Recent observations have revealed recruitment of the host GTPase Rab1 to the LCV by a process requiring the Dot/Icm system8,
9. Here, a visual screen was used to identify L. pneumophila mutants with defects in Rab1 recruitment. One of the factors identified in this screen was DrrA, a new Dot/Icm substrate protein translocated into host cells. We show that DrrA is a potent and highly specific Rab1 guanine nucleotide-exchange factor (GEF). DrrA can disrupt Rab1-mediated secretory transport to the Golgi apparatus by competing with endogenous exchange factors to recruit and activate Rab1 on plasma membrane-derived organelles. These data establish that intracellular pathogens have the capacity to directly modulate the activation state of a specific member of the Rab family of GTPases and thus further our understanding of the mechanisms used by bacterial pathogens to manipulate host vesicular transport.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated. NEWS AND VIEWSResearch HighlightsNature Structural & Molecular Biology News and Views (01 Nov 2007)
|
