title: The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor.
abstract: The intracellular pathogen Legionella pneumophila avoids fusion with lysosomes and subverts membrane transport from the endoplasmic reticulum to create an organelle that supports bacterial replication. 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/Icm. Recent observations have revealed recruitment of the host GTPase Rab1 to the LCV by a process requiring the Dot/Icm system. 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.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Murata
authors.forename: Anna
authors.initials: A
authors.lastname: Delprato
authors.forename: Alyssa
authors.initials: A
authors.lastname: Ingmundson
authors.forename: Derek K
authors.initials: DK
authors.lastname: Toomre
authors.forename: David G
authors.initials: DG
authors.lastname: Lambright
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009154:Mutation; D021381:Protein Transport; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology; D020761:rab1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C101895:DrrA protein, Bacteria; D020662:Guanine Nucleotide Exchange Factors; D020761:rab1 GTP-Binding Proteins