title: Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila.
abstract: The intracellular pathogen Legionella pneumophila replicates in a vacuole that recruits material from the host cell endoplasmic reticulum (ER). Biogenesis of this unique vacuole depends on the bacterial Dot/Icm type IV secretion system that translocates proteins across host cell membranes. Here, we show that two translocated substrates, SidM and LidA, target host cell Rab1, a small GTPase regulating ER-to-Golgi traffic. SidM is a guanosine nucleotide exchange factor for Rab1 that recruits Rab1 to Legionella-containing vacuoles, a process that is enhanced by LidA. Expression of sidM in mammalian cells interferes with the secretory pathway and causes Golgi fragmentation. Consistent with a collaborative relationship between the two proteins, immobilized SidM and LidA synergize to promote Rab1-dependent binding of early secretory vesicles. These results indicate that proteins translocated into the host cell by the intravacuolar pathogen L. pneumophila are able to recapitulate events involved in host secretory trafficking.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Machner
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001693:Biological Transport, Active; D002460:Cell Line; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008854:Microscopy, Electron; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000201:enzymology / Q000382:microbiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020761:rab1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020693:rab2 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D011994:Recombinant Proteins; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins; D020693:rab2 GTP-Binding Protein