Featured Publications
The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs
Horenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP, Shteyn V, Roy CR, Melia TJ, Reinisch KM. The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Developmental Cell 2015, 34: 569-576. PMID: 26343456, PMCID: PMC4594837, DOI: 10.1016/j.devcel.2015.08.010.Peer-Reviewed Original ResearchConceptsATG8 proteinsIntracellular pathogen Legionella pneumophilaPre-autophagosomal structureAtg8/LC3 proteinsPathogen Legionella pneumophilaHigh-curvature membranesMembrane transport pathwaysCytosol of cellsEffector proteinsCatalytic domainHost cytosolRavZAutophagy proteinsLC3 proteinPathogenic microbesSubstrate affinityProteinIntermediate membraneLegionella pneumophilaAutophagosomesAutophagyCytosolTransport pathwaysInterfacial activationMembraneAMPylation Is Critical for Rab1 Localization to Vacuoles Containing Legionella pneumophila
Hardiman CA, Roy CR. AMPylation Is Critical for Rab1 Localization to Vacuoles Containing Legionella pneumophila. MBio 2014, 5: 10.1128/mbio.01035-13. PMID: 24520063, PMCID: PMC3950522, DOI: 10.1128/mbio.01035-13.Peer-Reviewed Original ResearchConceptsLCV membraneEffector proteinsGEF activityEndoplasmic reticulumIntracellular pathogen Legionella pneumophilaLegionella effector proteinsType IV secretion systemExchange factor domainLegionella pneumophilaMembrane-bound compartmentsMembrane-bound organellesPathogen Legionella pneumophilaAccumulation of GTPHost cell functionsAMPylation activityDrrA proteinRab1 proteinRab1 recruitmentLegionella effectorsNucleotidyltransferase domainAMPylationSecretion systemPosttranslational modificationsRab1GTPaseLegionella pneumophila proteins that regulate Rab1 membrane cycling
Ingmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 2007, 450: 365-369. PMID: 17952054, DOI: 10.1038/nature06336.Peer-Reviewed Original ResearchConceptsDrrA proteinRab1 functionMembrane cyclingGTPase-activating protein activityIntracellular pathogen Legionella pneumophilaRecruitment of Rab1Pathogen-occupied vacuolesPathogen Legionella pneumophilaDistinct biochemical reactionsL. pneumophilaLegionella pneumophilaRab1 activityRab1 activationRab proteinsEukaryotic cellsExchange factorGTP hydrolysisProtein activityRab1Membrane functionBacterial replicationProteinBiochemical reactionsPneumophilaVacuolesAnkyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors
Pan X, Lührmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors. Science 2008, 320: 1651-1654. PMID: 18566289, PMCID: PMC2514061, DOI: 10.1126/science.1158160.Peer-Reviewed Original ResearchConceptsSecretion systemL. pneumophila-containing vacuoleIntracellular pathogen Legionella pneumophilaHost cellsDifferent bacterial proteinsType IV secretion systemMicrotubule-dependent vesicular transportEukaryotic host cellsType IV effectorsPathogen Legionella pneumophilaSpecialized secretion systemsAnkyrin Repeat ProteinsANK proteinsEukaryotic cellsHomology domainEffector proteinsEukaryotic factorsRepeat proteinsInfection of macrophagesVesicular transportBacterial proteinsLate endosomesDiverse familyProteinLegionella pneumophilaHost SNAREs mediate fusion of vacuoles containing Legionella pneumophila with vesicles exiting the endoplasmic reticulum
Arasaki K, Roy C. Host SNAREs mediate fusion of vacuoles containing Legionella pneumophila with vesicles exiting the endoplasmic reticulum. The FASEB Journal 2009, 23: 867.4-867.4. DOI: 10.1096/fasebj.23.1_supplement.867.4.Peer-Reviewed Original ResearchPlasma membrane-derived vacuoleEarly secretory vesiclesSNARE complexSNARE proteinsSecretory vesiclesPlasma membrane t-SNAREFunctional SNARE complexesPlasma membrane syntaxinsEndoplasmic reticulum-derived vesiclesLegionella pneumophilaT-SNAREsSyntaxin 4Mechanism of fusionSpecialized organellesSyntaxin 2Syntaxin 3Mammalian cellsEndoplasmic reticulumSec22bSNAP23SyntaxinBacterial uptakeLocalization studiesIntracellular pathogensBacterial replicationModulation of Rab GTPase function by a protein phosphocholine transferase
Mukherjee S, Liu X, Arasaki K, McDonough J, Galán JE, Roy CR. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature 2011, 477: 103-106. PMID: 21822290, PMCID: PMC3206611, DOI: 10.1038/nature10335.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsChlorocebus aethiopsCOS CellsDiacylglycerol CholinephosphotransferaseGuanine Nucleotide Exchange FactorsHEK293 CellsHost-Pathogen InteractionsHumansLegionella pneumophilaLegionnaires' DiseaseMass SpectrometryProtein Processing, Post-TranslationalRab GTP-Binding ProteinsThe Legionella pneumophila Effector DrrA Is Sufficient to Stimulate SNARE-Dependent Membrane Fusion
Arasaki K, Toomre DK, Roy CR. The Legionella pneumophila Effector DrrA Is Sufficient to Stimulate SNARE-Dependent Membrane Fusion. Cell Host & Microbe 2012, 11: 46-57. PMID: 22264512, PMCID: PMC3266541, DOI: 10.1016/j.chom.2011.11.009.Peer-Reviewed Original ResearchConceptsMembrane transport pathwaysEndoplasmic reticulumSyntaxin proteinsFusion of ERMembrane fusionSNARE-dependent membrane fusionBacterial pathogen Legionella pneumophilaPathogen-containing vacuolesSNARE protein Sec22bIntracellular bacterial pathogen Legionella pneumophilaPathogen Legionella pneumophilaFusion of vesiclesRab1 activationNoncanonical pairingTransport pathwaysRab1 GTPasePlasma membraneVesicle fusionOrganellesDrrASec22bVesiclesLegionella pneumophilaProteinVacuolesThe Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation
Choy A, Dancourt J, Mugo B, O’Connor T, Isberg RR, Melia TJ, Roy CR. The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation. Science 2012, 338: 1072-1076. PMID: 23112293, PMCID: PMC3682818, DOI: 10.1126/science.1227026.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAutophagyAutophagy-Related Protein 7Autophagy-Related Protein 8 FamilyAutophagy-Related ProteinsBacterial ProteinsCell Culture TechniquesCysteine ProteasesGene DeletionGlycineHEK293 CellsHost-Pathogen InteractionsHumansHydrolysisLegionella pneumophilaLegionnaires' DiseaseMicrofilament ProteinsPhagosomesUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesConceptsATG8 proteinsIntracellular pathogen Legionella pneumophilaPathogen Legionella pneumophilaAdjacent aromatic residuesCarboxyl-terminal glycine residueAutophagosome membraneEukaryotic cellsAutophagy pathwayGlycine residueAromatic residuesIntracellular pathogensRavZAutophagyProteinLegionella pneumophilaSpecific mechanismsResiduesPathogensATG3MicrobesAtg7CytosolVacuolesPathwayPneumophilaCaspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila
Case CL, Kohler LJ, Lima JB, Strowig T, de Zoete MR, Flavell RA, Zamboni DS, Roy CR. Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1851-1856. PMID: 23307811, PMCID: PMC3562791, DOI: 10.1073/pnas.1211521110.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAnimalsApoptosisApoptosis Regulatory ProteinsBone Marrow CellsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CaspasesCaspases, InitiatorCells, CulturedCytokinesCytoskeletal ProteinsEnzyme ActivationFlagellinHost-Pathogen InteractionsImmunoblottingLegionella pneumophilaMacrophagesMiceMice, Inbred C57BLMice, KnockoutMutationMyeloid Differentiation Factor 88NecrosisNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Interferon alpha-betaConceptsCaspase-11 activationCaspase-11Intracellular pathogen Legionella pneumophilaType IV secretion systemDot/IcmAdapter protein TRIFFunctional type IV secretion systemPathogen Legionella pneumophilaCaspase-1 activation pathwayNAIP/NLRC4Activation pathwayLegionella pneumophilaCaspase-11-dependent pyroptosisSecretion systemSevere defectsBacterial flagellinTreatment of macrophagesType I IFN receptorHost componentsIntracellular pathogensMicrobial signaturesPathwayIFN receptorCaspase-1Alternative pathway
2010
Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein
Lührmann A, Nogueira CV, Carey KL, Roy CR. Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18997-19001. PMID: 20944063, PMCID: PMC2973885, DOI: 10.1073/pnas.1004380107.Peer-Reviewed Original ResearchConceptsPathogen-induced apoptosisEffector proteinsMammalian hostsL. pneumophila effector proteinsType IV effector proteinsHost cellsType IV secretion systemMammalian host cellsL. pneumophilaGain of functionProtein repertoireOrganelle traffickingRepeat familyDistinct hostsSecretion systemInfection strategiesProtozoan hostsApoptosis pathwayIntracellular bacteriaIntracellular replicationVirulence determinantsProteinLegionella pneumophilaApoptosisPathogens
2006
Genetics of Mouse Macrophage Resistance to Legionella pneumophila
Vance R, Ren T, Zamboni D, Roy C, Dietrich W. Genetics of Mouse Macrophage Resistance to Legionella pneumophila. 2006, 301-306. DOI: 10.1128/9781555815660.ch73.Peer-Reviewed Original ResearchB6 macrophagesRapid cell deathMacrophage resistanceBacterial geneticsProtein kinaseNod proteinsLegionella replicationGenetic studiesPutative ligandCell deathProtein 5Intracellular receptorsGeneticsMouse macrophagesLegionella pneumophilaBiological relationshipsPowerful approachFlagellinJ macrophagesNAIPLegionella growthKnockout miceConcerted applicationMacrophagesImmune systemUtilization of Endoplasmic Reticulum Membranes to Establish a Vacuole that Supports Replication of Legionella pneumophila
Stein M, Roy C. Utilization of Endoplasmic Reticulum Membranes to Establish a Vacuole that Supports Replication of Legionella pneumophila. 2006, 199-210. DOI: 10.1002/352760880x.ch11.Peer-Reviewed Original ResearchAutophagy machineryAutophagy mutantsHost autophagy machineryAutophagosome maturationMorphological differencesOther BacteriaLegionella replicationAutophagy formationEndoplasmic reticulum membraneReticulum membraneMutantsAutophagosomesMachineryAutophagyBiogenesisLegionella pneumophilaVacuolesBacteriaReplicationLCVMaturationLegionellaInduction
2001
How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane.
Tilney L, Harb O, Connelly P, Robinson C, Roy C. How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane. Journal Of Cell Science 2001, 114: 4637-50. PMID: 11792828, DOI: 10.1242/jcs.114.24.4637.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsCarrier ProteinsCell FractionationCell MembraneGram-Positive BacteriaHumansIntracellular MembranesLegionella pneumophilaLipid MetabolismLysosomesMembrane ProteinsMicroscopy, ElectronMitochondriaMolecular ChaperonesMutationOrganellesPhagosomesRibosomesTime FactorsU937 CellsConceptsPhagosomal membraneRough endoplasmic reticulumRough ERL. pneumophilaL. pneumophila mutantsBacterium Legionella pneumophilaMinutes of infectionLegionella pneumophilaInfected macrophagesER membraneCellular processesMitochondrial membranePlasma membraneER vesiclesEndoplasmic reticulumMacrophage infectionPhagosomesLack of cholesterolMitochondriaPneumophilaMembraneTiny hairsERMutantsThe DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter
Nagai H, Roy C. The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. The EMBO Journal 2001, 20: 5962-5970. PMID: 11689436, PMCID: PMC125688, DOI: 10.1093/emboj/20.21.5962.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacterial ProteinsBiological TransportCarrier ProteinsCell MembraneCulture Media, ConditionedElectrophoresis, Polyacrylamide GelHost-Parasite InteractionsImmunoblottingLegionella pneumophilaMacromolecular SubstancesMembrane ProteinsMolecular Sequence DataOrganellesSequence Analysis, ProteinConceptsDot/icm genesDotA proteinIcm genesDot/Icm transporterPolytopic membrane proteinsDot/IcmEukaryotic host cellsN-terminal sequencingAmino acid leader peptideLegionella pneumophilaSecretion apparatusMembrane proteinsLeader peptideMembrane vesiclesProtein secretionHost cellsProteinBacterial replicationGenesTransportersPneumophilaUnique processOrganellesCulture supernatantsSecretion
2000
Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth
Coers J, Kagan J, Matthews M, Nagai H, Zuckman D, Roy C. Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Molecular Microbiology 2000, 38: 719-736. PMID: 11115108, DOI: 10.1046/j.1365-2958.2000.02176.x.Peer-Reviewed Original ResearchConceptsPhagosome traffickingTransport apparatusHost cellsProtein-protein interactionsSubset of genesGel overlay analysisDistinct phenotypic categoriesPhagocytic host cellsIcm genesTranslocation channelReplicative organelleTwo-hybridProtein complexesSpecialized organellesTransporter functionIntracellular growthMolecular levelDistinct rolesVirulence determinantsGenesPore formationBacterial pathogensBiogenesisPhenotypic categoriesLegionella pneumophila
1999
Pore‐forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth
Zuckman D, Hung J, Roy C. Pore‐forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth. Molecular Microbiology 1999, 32: 990-1001. PMID: 10361301, DOI: 10.1046/j.1365-2958.1999.01410.x.Peer-Reviewed Original ResearchConceptsPhagosome traffickingPhagosome-lysosome fusionIntracellular growthLysosome fusionEukaryotic cellular processesInsertion of poresPore-forming activityL. pneumophila mutantsHost cell cytoplasmCellular processesMammalian cellsReplicative nicheSimilar cytolytic activityGene productsPhagosome membraneIntracellular bacteriaTraffickingCell cytoplasmEffector moleculesBacterial pathogensLegionella pneumophilaMacrophage membraneVirulent bacteriaBacteriaFusion inhibition