2025
Mutations in the SWEET15 Sugar Transporter Gene Affect Response of Citrus to Huanglongbing Disease and Citrus Canker
Khadgi A, Zayed O, Sagawa C, Zhang F, Seymour D, Irish V. Mutations in the SWEET15 Sugar Transporter Gene Affect Response of Citrus to Huanglongbing Disease and Citrus Canker. Molecular Plant Pathology 2025, 26: e70094. PMID: 40369935, PMCID: PMC12078760, DOI: 10.1111/mpp.70094.Peer-Reviewed Original ResearchConceptsSecretion systemCitrus cankerSusceptibility genesEffector proteinsType III secretion systemSec secretion systemIII secretion systemBacterial secretion systemsBacterial diseasesXanthomonas citri pvSusceptibility to citrus cankerCitrus cultivarsCandidatus Liberibacter asiaticusSusceptibility gene expressionPlant immunityInfected plantsBacterial pathogensSucrose transportGene activationLiberibacter asiaticusPromote pathogenesisExported TransportersSWEET15Lemon plantsCanker
2024
The T4bSS of Legionella features a two-step secretion pathway with an inner membrane intermediate for secretion of transmembrane effectors
Malmsheimer S, Grin I, Bohn E, Franz-Wachtel M, Macek B, Sahr T, Smollich F, Chetrit D, Meir A, Roy C, Buchrieser C, Wagner S. The T4bSS of Legionella features a two-step secretion pathway with an inner membrane intermediate for secretion of transmembrane effectors. PLOS Pathogens 2024, 20: e1012118. PMID: 39546547, PMCID: PMC11602083, DOI: 10.1371/journal.ppat.1012118.Peer-Reviewed Original ResearchConceptsEukaryotic host cellsEffector proteinsMembrane intermediatesC-terminal secretion signalHost cellsSoluble effector proteinsCytoplasmic sideBacterial inner membraneMechanism of secretionSecretion systemSecretion signalPeriplasmic loopTransmembrane effectorSecretion pathwayT4BSSInner membraneSubcellular locationIntracellular survivalMembrane targetingProtein complexesEfficient translocationBacterial cellsProteomic analysisL. pneumophilaSecretion processNotch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching
Raza Q, Nadeem T, Youn S, Swaminathan B, Gupta A, Sargis T, Du J, Cuervo H, Eichmann A, Ackerman S, Naiche L, Kitajewski J. Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching. Scientific Reports 2024, 14: 13603. PMID: 38866944, PMCID: PMC11169293, DOI: 10.1038/s41598-024-64375-z.Peer-Reviewed Original ResearchConceptsNotch signalingEndothelial cell behaviorEndothelial junctionsCell behaviorMultiple endothelial cell typesStabilization of endothelial junctionsNotch activationEndothelial Notch signalingTarget of Notch signalingTranscriptional activation complexEndothelial cell typesPlexus branchesVascular densityEndothelial proliferationBrain endotheliumMouse retinaIn vivo targetingEffector proteinsVascular outgrowthJunction activityNotch proteinsEndothelial cellsExcessive vascularizationDownstream effectorsEndothelial gene expression
2023
The Coxiella burnetii effector EmcB is a deubiquitinase that inhibits RIG-I signaling
Duncan-Lowey J, Crabill E, Jarret A, Reed S, Roy C. The Coxiella burnetii effector EmcB is a deubiquitinase that inhibits RIG-I signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2217602120. PMID: 36893270, PMCID: PMC10089202, DOI: 10.1073/pnas.2217602120.Peer-Reviewed Original ResearchConceptsDot/Icm systemHost-adapted pathogenUbiquitin chainsI interferon productionType I interferon productionSecretion systemHost cytosolIcm systemInterferon productionProtein secretion systemBacterial secretion systemsAcid-inducible gene IHost surveillance systemImmune sensorsObligate intracellular pathogensInducible gene ICytosolic surveillance systemsProtective immune responseEffector proteinsSpecialized organellesVacuolar nicheInhibition of RIGInnate immune sensorsSurveillance systemMammalian hosts
2022
Development of an Accessible Gene Expression Bioinformatics Pipeline to Study Driver Mutations of Colorectal Cancer
van den Driest L, Johnson CH, Rattray NJW, Rattray Z. Development of an Accessible Gene Expression Bioinformatics Pipeline to Study Driver Mutations of Colorectal Cancer. Alternatives To Laboratory Animals 2022, 50: 282-292. PMID: 35765262, DOI: 10.1177/02611929221107546.Peer-Reviewed Original ResearchConceptsColorectal cancerBioinformatics toolsExpression patternsKirsten rat sarcoma viral oncogene homologueNext-generation sequencing technologiesDifferential expression patternsCancer-related mortalityGenetic alterationsAdenomatous polyposis coliEffector proteinsMutational driversPrognostic significancePrognostic valueSequencing technologiesBioinformatics pipelinePatient prognosisGenetic dataB-RafColorectal tumorsNovel biomarkersColon cancerTherapeutic outcomesFrequency of mutationsAnatomical locationOncogene homologue
2021
A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides
Li JH, Cho W, Hamchand R, Oh J, Crawford JM. A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides. Journal Of Natural Products 2021, 84: 2692-2699. PMID: 34581573, PMCID: PMC9970011, DOI: 10.1021/acs.jnatprod.1c00573.Peer-Reviewed Original ResearchConceptsNonribosomal peptide synthetasePeptide synthetaseBiosynthetic gene clusterComparative genomic analysisFree-living infective juvenilesNRPS genesEffector proteinsInsect larvaeSpecialized metabolitesGene clusterMutualistic relationshipXenorhabdus bovieniiHeterologous expressionGenomic analysisRichest producersEntomopathogenic bacteriumSecondary metabolitesHost larvaeInfective juvenilesTermination domainInhibitor pathwayExogenous alcoholsLarvaeSpeciesComplex arrayComposition and Biophysical Properties of the Sorting Platform Pods in the Shigella Type III Secretion System
Tachiyama S, Skaar R, Chang Y, Carroll BL, Muthuramalingam M, Whittier SK, Barta ML, Picking WL, Liu J, Picking WD. Composition and Biophysical Properties of the Sorting Platform Pods in the Shigella Type III Secretion System. Frontiers In Cellular And Infection Microbiology 2021, 11: 682635. PMID: 34150677, PMCID: PMC8211105, DOI: 10.3389/fcimb.2021.682635.Peer-Reviewed Original ResearchConceptsType III secretion systemCytoplasmic sorting platformSorting platformSecretion systemTwo-hybrid analysisCryo-electron tomography dataC-terminal domainShigella type III secretion systemFull-length copiesBiophysical propertiesDistinct biophysical propertiesSpa47 ATPaseT3SS injectisomeEffector proteinsSecretion substratesDistinct complexesIntracellular nicheBasal bodiesPrimary virulence factorSpa33Host cellsHeterotrimerPrecise makeupVirulence factorsMxiKCoxiella burnetii encodes an LvgA‐related protein important for intracellular replication
Steiner S, Meir A, Roy CR. Coxiella burnetii encodes an LvgA‐related protein important for intracellular replication. Cellular Microbiology 2021, 23: e13331. PMID: 33774901, DOI: 10.1111/cmi.13331.Peer-Reviewed Original ResearchConceptsIntracellular replicationDot/Icm type IVB secretion systemType IVB secretion systemDot/Icm apparatusHost cell cytosolTransposon mutagenesis screenAutophagy protein LC3Lysosome-derived organellesL. pneumophilaSecondary structure predictionChaperone complexBiogenesis defectsEffector proteinsEffector translocationProtein complexesMutagenesis screenSecretion systemLvgACell cytosolNine Mile phase IIProtein LC3MutantsReplication phenotypeProteinStructure prediction
2019
The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells
Lara-tejero M, Galán J. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells. 2019, 245-259. DOI: 10.1128/9781683670285.ch20.Peer-Reviewed Original ResearchSecretion machineType III protein secretion systemType III secretion machinesProtein secretion systemTarget eukaryotic cellsCell biological processesType III systemMultiprotein nanomachineEukaryotic hostsComplex nanomachinesGram-negative bacteriaPlant pathogensSymbiotic interactionsEukaryotic cellsEffector proteinsSecretion systemMammalian cellsImportant humanBiological processesStructural organizationInjectisomeBacteriaCurrent knowledgeCentral rolePrimary functionThe Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells
Lara-Tejero M, Galán JE. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells. EcoSal Plus 2019, 8: 10.1128/ecosalplus.esp-0039-2018. PMID: 30942149, PMCID: PMC6450406, DOI: 10.1128/ecosalplus.esp-0039-2018.Peer-Reviewed Original ResearchConceptsEffector proteinsGram-negative bacteriaSecretion systemBacterial envelopeType III protein secretion systemProtein secretion systemHost cellular functionsEukaryotic plasma membraneEukaryotic cell membranesHost cell cytosolMultiprotein nanomachineEukaryotic hostsComplex nanomachinesImportant bacterial pathogensCellular functionsMammalian cellsNeedle complexOuter membranePlasma membraneCell cytosolInjectisomeCell membraneProteinBacterial pathogensCentral role
2018
Visualization of the type III secretion mediated Salmonella–host cell interface using cryo-electron tomography
Park D, Lara-Tejero M, Waxham MN, Li W, Hu B, Galán JE, Liu J. Visualization of the type III secretion mediated Salmonella–host cell interface using cryo-electron tomography. ELife 2018, 7: e39514. PMID: 30281019, PMCID: PMC6175578, DOI: 10.7554/elife.39514.Peer-Reviewed Original ResearchConceptsCryo-electron tomographyEffector translocationBacterial-host cell contactType III protein secretion systemProtein secretion systemHost cell interfaceProtein secretion machinesCell membraneComplex host-pathogen interactionsType III secretionHost-pathogen interactionsHost cell membraneTarget cell membraneNegative bacterial pathogensTranslocon poreSecretion machineEffector proteinsSecretion systemHost cellsBacterial pathogensCell contactCell interfaceIntimate associationTranslocationBacteriaSalmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors
Sun H, Kamanova J, Lara-Tejero M, Galán JE. Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors. Nature Microbiology 2018, 3: 1122-1130. PMID: 30224799, PMCID: PMC6158040, DOI: 10.1038/s41564-018-0246-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial Loadcdc42 GTP-Binding ProteinCells, CulturedHost-Pathogen InteractionsHumansImmunity, InnateIntestinesMAP Kinase Kinase KinasesMiceNF-kappa Bp21-Activated KinasesPhosphorylationSalmonella InfectionsSalmonella typhimuriumSignal TransductionTNF Receptor-Associated Factor 6Type III Secretion SystemsConceptsP21-activated kinase 1TNF Receptor-Associated Factor 6Innate immune receptorsImmune receptorsType III protein secretion systemMitogen-activated protein kinase kinase kinase 7Protein kinase kinase kinase 7Protein secretion systemPro-inflammatory signalingP21-activated kinaseNegative regulatory mechanismsEnteric pathogen Salmonella typhimuriumPathogen Salmonella typhimuriumIntestinal inflammationMicrobial productsEffector proteinsS. typhimuriumSecretion systemInflammatory signalingRegulatory mechanismsKinase 1Kinase 7PAK inhibitorsCritical downstreamResident microbiotaThe N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase
Stiegler AL, Boggon TJ. The N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase. Structure 2018, 26: 1451-1461.e4. PMID: 30174148, PMCID: PMC6249675, DOI: 10.1016/j.str.2018.07.015.Peer-Reviewed Original ResearchConceptsP190RhoGAP proteinsN-terminal GTPase domainProtein-protein interaction domainsNucleotide exchange factorsCanonical GTPaseGTPase domainKnown proteinsEffector proteinsExchange factorInteraction domainNucleotide bindingMutational analysisCritical regulatorGTP-MgGTPProteinBiochemical analysisImportant groupBindingDomainPseudoenzymesGTPaseRestraining Akt1 Phosphorylation Attenuates the Repair of Radiation-Induced DNA Double-Strand Breaks and Reduces the Survival of Irradiated Cancer Cells
Szymonowicz K, Oeck S, Krysztofiak A, van der Linden J, Iliakis G, Jendrossek V. Restraining Akt1 Phosphorylation Attenuates the Repair of Radiation-Induced DNA Double-Strand Breaks and Reduces the Survival of Irradiated Cancer Cells. International Journal Of Molecular Sciences 2018, 19: 2233. PMID: 30065170, PMCID: PMC6121313, DOI: 10.3390/ijms19082233.Peer-Reviewed Original ResearchConceptsDSB repairLong-term colony formation assaysDNA double-strand break repairDouble-strand break repairKinase-protein kinase BPhosphorylation-deficient mutantKey phosphorylation sitesDNA damage responseEssential subcellular processesProtein kinase BDSB repair kineticsCancer cellsCellular radiation responseActivation stateMurine prostate cancer cellsColony formation assaysEffector proteinsGenotoxic stressPhosphorylation sitesDamage responseBreak repairGenetic approachesThreonine 308Serine 473Kinase B
2017
Diverse Class 2 CRISPR-Cas Effector Proteins for Genome Engineering Applications
Pyzocha NK, Chen S. Diverse Class 2 CRISPR-Cas Effector Proteins for Genome Engineering Applications. ACS Chemical Biology 2017, 13: 347-356. PMID: 29121460, PMCID: PMC6768076, DOI: 10.1021/acschembio.7b00800.Peer-Reviewed Original ResearchConceptsGenome engineering applicationsCRISPR-Cas genome editing technologiesMicrobial adaptive immune systemGenome editing technologyEffector enzymeNucleic acid cleavageEditing technologyUnique propertiesModern molecular biologyEngineering applicationsEffector proteinsMammalian cellsMolecular biologyAdaptive immune systemWide diversityTechnologyEnzymeApplicationsFunctionalityAcid cleavageImmune systemBiologyProteinDNADiversityMultiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries
Shames SR, Liu L, Havey JC, Schofield WB, Goodman AL, Roy CR. Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e10446-e10454. PMID: 29133401, PMCID: PMC5715750, DOI: 10.1073/pnas.1708553114.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCytotoxicity, ImmunologicDisease Models, AnimalFemaleGene Expression Regulation, BacterialHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansLegionella pneumophilaLegionnaires' DiseaseLoss of Function MutationMiceMice, Inbred C57BLMutagenesis, InsertionalPhenotypeVirulenceConceptsCultured host cellsHost cellsEffector proteinsHost immune systemFunction mutationsVirulence phenotypesSevere pneumoniaInfected miceBacterial clearanceEffector mutantsLarge cohortMouse modelDot/Icm type IV secretion systemImmune systemType IV secretion systemScreen resultsEffector protein activityDifferent effector proteinsGenetic complementation studiesLegionnaires' diseaseCausative agentHost pathogenesisDifferent virulence phenotypesInfectionDiseaseVisualization and characterization of individual type III protein secretion machines in live bacteria
Zhang Y, Lara-Tejero M, Bewersdorf J, Galán JE. Visualization and characterization of individual type III protein secretion machines in live bacteria. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 6098-6103. PMID: 28533372, PMCID: PMC5468683, DOI: 10.1073/pnas.1705823114.Peer-Reviewed Original ResearchConceptsProtein secretion machinesSecretion machineType III secretion machinesLive bacteriaEukaryotic cellsEffector proteinsMolecular machinesSubcellular distributionSuperresolution microscopyBacteriaMajor insightsResolution gapDetailed viewAssemblyMutantsProteinNanomachinesCharacterizationCellsSpatial distributionIsolation
2016
A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis
Sun H, Kamanova J, Lara-Tejero M, Galán JE. A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis. PLOS Pathogens 2016, 12: e1005484. PMID: 26933955, PMCID: PMC4775039, DOI: 10.1371/journal.ppat.1005484.Peer-Reviewed Original ResearchConceptsNF-κBHost homeostasisNF-κB Signaling PathwayHost innate immune responsePro-inflammatory cytokinesInnate immune responseType III secretion effector proteinsHost tissue damageIntestinal inflammationSalmonella typhimurium strainsImmune responseAnimal modelsInflammationRelB transcription factorPathogen replicationMicrobial infectionsTyphimurium strainsEffector proteinsSignaling pathwaysType III secretion systemInfectionBacterial pathogensBacteria Salmonella typhimuriumSignal transduction pathwaysSalmonella typhimurium
2015
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 activationMembraneAltered Expression of CDC42 Signaling Pathway Components in Cortical Layer 3 Pyramidal Cells in Schizophrenia
Datta D, Arion D, Corradi J, Lewis D. Altered Expression of CDC42 Signaling Pathway Components in Cortical Layer 3 Pyramidal Cells in Schizophrenia. Biological Psychiatry 2015, 78: 775-785. PMID: 25981171, PMCID: PMC4600637, DOI: 10.1016/j.biopsych.2015.03.030.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntipsychotic AgentsBenzodiazepinescdc42 GTP-Binding ProteinCytoskeletal ProteinsFemaleGene Expression RegulationGTP-Binding Protein RegulatorsHaloperidolHumansLaser Capture MicrodissectionLim KinasesMacaca fascicularisMaleMiddle AgedOlanzapinep21-Activated KinasesPrefrontal Cortexrho GTP-Binding Proteinsrho Guanine Nucleotide Dissociation Inhibitor alphaRNA-Binding ProteinsSchizophreniaSignal TransductionConceptsSerine/threonine protein kinaseThreonine protein kinaseActin cytoskeletonProtein kinaseCdc42 effector proteinsCell type-specific fashionMessenger RNA levelsCell division cycle 42Altered expressionType-specific fashionDLPFC gray matterRNA levelsEffector proteinsActin dynamicsPathway componentsSame transcriptKey organizerMessenger RNALaser microdissectionSynergistic alterationsCdc42CytoskeletonQuantitative polymerase chain reactionSpine formationKinase
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