title: Legionella pneumophila proteins that regulate Rab1 membrane cycling.
abstract: Rab1 is a GTPase that regulates the transport of endoplasmic-reticulum-derived vesicles in eukaryotic cells. The intracellular pathogen Legionella pneumophila subverts Rab1 function to create a vacuole that supports bacterial replication by a mechanism that is not well understood. Here we describe L. pneumophila proteins that control Rab1 activity directly. We show that a region in the DrrA (defect in Rab1 recruitment A) protein required for recruitment of Rab1 to membranes functions as a guanine nucleotide dissociation inhibitor displacement factor. A second region of the DrrA protein stimulated Rab1 activation by functioning as a guanine nucleotide exchange factor. The LepB protein was found to inactivate Rab1 by stimulating GTP hydrolysis, indicating that LepB has GTPase-activating protein activity that regulates removal of Rab proteins from membranes. Thus, L. pneumophila encodes proteins that regulate three distinct biochemical reactions critical for Rab GTPase membrane cycling to redirect Rab1 to the pathogen-occupied vacuole and to control Rab1 function.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Ingmundson
authors.forename: Anna
authors.initials: A
authors.lastname: Delprato
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*; D001692:Biological Transport; D002460:Cell Line; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology; D020761:rab1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020690:GTPase-Activating Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; C482639:LepB protein, Legionella pneumophila; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020761:rab1 GTP-Binding Proteins