2025
A flexible peptide linking the periplasmic and cytoplasmic domains of MxiG controls type III secretion signaling and stable sorting platform assembly in Shigella
Tachiyama S, Muthuramalingam M, Whittier S, Chang Y, Yue J, Younis W, Picking W, Liu J, Picking W. A flexible peptide linking the periplasmic and cytoplasmic domains of MxiG controls type III secretion signaling and stable sorting platform assembly in Shigella. Frontiers In Cellular And Infection Microbiology 2025, 15: 1611779. PMID: 40831705, PMCID: PMC12358396, DOI: 10.3389/fcimb.2025.1611779.Peer-Reviewed Original ResearchConceptsSorting platformSecretion signalCytoplasmic domainLinker peptideType III secretion systemType III secretion signalInner membrane ringIII secretion systemHost cell contactLibrary of mutantsFlexible linker peptideCentral ATPaseT3SS functionSecretion systemVirulence functionsEffector proteinsPeriplasmic domainSecreted effectorsT3SS injectisomeAdaptor proteinMxiGNeedle formationTransmembrane helicesMembrane ringInjectisomeThe Roles of the Numb Protein in Synaptic Development and Plasticity
Sukhanova T, Renkemeyer M, Pritchett N, Berke B, Keshishian H. The Roles of the Numb Protein in Synaptic Development and Plasticity. Developmental Neurobiology 2025, 85: e22988. PMID: 40620134, PMCID: PMC12258135, DOI: 10.1002/dneu.22988.Peer-Reviewed Original ResearchConceptsLarval neuromuscular junctionGrowth factor signalingEndocytic processRNAi knockdownNumb proteinFactor signalingDrosophila neuromuscular junctionSynaptic developmentKnockdown of NumbGrowth factor receptor signalingNeuromuscular junctionGenetic interactionsAdaptor proteinGrowth plasticityLoss of functionPresynaptic sidePresynaptic boutonsReceptor signalingGrowth factor receptorProteinFactor receptorLarvalGrowthAdaptorRNAiRBX1-Cullin RING Ubiquitin Ligases Are Indispensable For Perinatal Cardiac Development Through Regulating The Hippo-YAP Signaling Pathway
Zambrano-Carrasco J, Jiao K, Li J, Su H. RBX1-Cullin RING Ubiquitin Ligases Are Indispensable For Perinatal Cardiac Development Through Regulating The Hippo-YAP Signaling Pathway. Physiology 2025, 40: 0183. DOI: 10.1152/physiol.2025.40.s1.0183.Peer-Reviewed Original ResearchCullin-RING ubiquitin E3 ligasesCullin proteinsCardiac morphologic abnormalitiesHippo-YAPCardiac morphogenesisCardiac developmentDosage-sensitive regulatorRING ubiquitin ligasesMulti-subunit complexesTranscriptional regulatory mechanismsUbiquitin E3 ligaseHippo-YAP signaling pathwayHippo-YAP pathwayRegulation of cardiac morphogenesisHeart failureDefective cardiac developmentExpression of genesMammalian heart developmentCardiomyocyte proliferationCell autonomous roleHypoplastic ventricular myocardiumVentricular chamber developmentAdaptor proteinCullin-RINGBiventricular non-compaction
2024
AP2A2 mutation and defective endocytosis in a Malian family with hereditary spastic paraplegia
Diarra S, Ghosh S, Cissé L, Coulibaly T, Yalcouyé A, Harmison G, Diallo S, Diallo S, Coulibaly O, Schindler A, Cissé C, Maiga A, Bamba S, Samassekou O, Khokha M, Mis E, Lakhani S, Donovan F, Jacobson S, Blackstone C, Guinto C, Landouré G, Bonifacino J, Fischbeck K, Grunseich C. AP2A2 mutation and defective endocytosis in a Malian family with hereditary spastic paraplegia. Neurobiology Of Disease 2024, 198: 106537. PMID: 38772452, PMCID: PMC11209852, DOI: 10.1016/j.nbd.2024.106537.Peer-Reviewed Original ResearchHereditary spastic paraplegiaPatient-derived neuronsAdaptor proteinEndocytosis of transferrin receptorsSpastic paraplegiaXenopus tropicalis tadpolesNeuronal cellsHomozygous missense variantWhole-exome sequencingMalian familyComplicated hereditary spastic paraplegiaMissense variantsExome sequencingAccessory proteinsGroup of neurogenetic disordersDefective endocytosisWestern blot analysisProgressive lower extremity spasticityGenetic diagnosisGenetic testingBlot analysisAP2A2Neurological evaluationFrog modelEndocytosisRBX1-CRLs Promote Perinatal Heart Development by Regulating Hippo-YAP Signaling
Zambrano-Carrasco J, Wang W, Ayala J, Sibley J, Carruth J, Jiao K, Li J, Su H. RBX1-CRLs Promote Perinatal Heart Development by Regulating Hippo-YAP Signaling. Physiology 2024, 39: 963. DOI: 10.1152/physiol.2024.39.s1.963.Peer-Reviewed Original ResearchCullin-RING E3 ubiquitin ligasesCongenital heart diseaseCardiomyocyte proliferationCardiac developmentNuclear translocation of YAPTransfer of ubiquitinMulti-subunit complexesE3 ubiquitin ligasePerinatal heart developmentTranslocation of YAPHippo-YAP signalingInactivation of YAPImpaired nuclear translocationCo-transcription factorCardiac malformationsMyocardial hypoplasiaPeripheral edemaAdaptor proteinCKO heartsCullin-RINGLittermate controlsProtein substratesEdU incorporation assayHippo kinasesProtein homeostasisCellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation
Ranjan K, Pathak C. Cellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation. International Journal Of Molecular Sciences 2024, 25: 3228. PMID: 38542202, PMCID: PMC10970579, DOI: 10.3390/ijms25063228.Peer-Reviewed Original ResearchConceptsFas-associated death domainDeath domainDeath receptorsInitiation of apoptotic signalingRegulate programmed cell deathExpression of Fas-associated death domainSignaling pathwayCellular dynamicsRegulator of inflammatory signalingRegulation of cancerAdaptor proteinActivated caspasesApoptotic functionApoptosis signalingSubcellular localizationApoptotic signalingCellular homeostasisCell deathCell survivalCoordinated removalCellular senescenceIntracellular expressionCell proliferationSpatiotemporal mechanismsInflammatory signaling
2022
The noncanonical inflammasome in health and disease
Cahoon J, Yang D, Wang P. The noncanonical inflammasome in health and disease. Infectious Medicine 2022, 1: 208-216. PMID: 38077630, PMCID: PMC10699704, DOI: 10.1016/j.imj.2022.09.001.Peer-Reviewed Original ResearchNoncanonical inflammasomeRapid cellular responsesKey cellular regulatorsInnate immune signalingMechanism of activationAdaptor proteinCellular regulatorsPattern recognition receptorsNon-canonical inflammasomeImmune signalingCaspase-4Cellular responsesRecognition receptorsSubsequent maturationNegative bacterial infectionsCaspase-1Inflammatory cytokinesInflammatory diseasesInflammasomeBacterial infectionsRecent advancesDiseaseSignalingRegulatorProteinRegulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli
Shu S, Mi W. Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli. Nature Communications 2022, 13: 4576. PMID: 35931690, PMCID: PMC9356133, DOI: 10.1038/s41467-022-32277-1.Peer-Reviewed Original ResearchConceptsRegulatory mechanismsAnti-adaptor proteinsFirst committed stepMost Gram-negative bacteriaEssential glycolipidEssential membraneGram-negative bacteriaTransmembrane helicesAdaptor proteinCommitted stepCytoplasmic domainFtsHLPS synthesisAnalysis unravelsLipopolysaccharide synthesisLapBEscherichia coliE. coliPermeability barrierProtein levelsLpxCProtease activityProteinColiYejMSequence Determinants of TDP-43 Ribonucleoprotein Condensate Formation and Axonal Transport in Neurons
Vishal SS, Wijegunawardana D, Salaikumaran MR, Gopal PP. Sequence Determinants of TDP-43 Ribonucleoprotein Condensate Formation and Axonal Transport in Neurons. Frontiers In Cell And Developmental Biology 2022, 10: 876893. PMID: 35646935, PMCID: PMC9133736, DOI: 10.3389/fcell.2022.876893.Peer-Reviewed Original ResearchAmyotrophic lateral sclerosisTDP-43A315TAxonal transportTDP-43 variantsMotor neuron degenerationTDP-43 mutationsNeuron degenerationLateral sclerosisTransport deficitsAnterograde transportNeuronsK mutationDisease-linked mutationsMotilityKey determinantPossible mechanismMutationsPrevious findingsRetrograde motilityTransport granulesAdaptor proteinSclerosisDeterminantsGranule transportThe role of FYCO1-dependent autophagy in lens fiber cell differentiation
Khan SY, Ali M, Kabir F, Na CH, Delannoy M, Ma Y, Qiu C, Costello MJ, Hejtmancik JF, Riazuddin SA. The role of FYCO1-dependent autophagy in lens fiber cell differentiation. Autophagy 2022, 18: 2198-2215. PMID: 35343376, PMCID: PMC9397473, DOI: 10.1080/15548627.2022.2025570.Peer-Reviewed Original ResearchConceptsAutophagic vesiclesLens fiber cell differentiationMouse lensesAutophagic fluxFiber cell differentiationHuman embryonic stem cellsCoiled-coil domainOrganelle-free zoneEmbryonic stem cellsHuman lens epithelial cellsAutophagy-associated genesSingle guide RNAsQuantitative real-time PCRLens epithelial cellsAdaptor proteinRNA-seqGuide RNARNA sequencingCellular organellesLens morphogenesisCataract phenotypeWild typeFYCO1Cell differentiationEndoplasmic reticulum
2021
PLCγ1 promotes phase separation of T cell signaling components
Zeng L, Palaia I, Šarić A, Su X. PLCγ1 promotes phase separation of T cell signaling components. Journal Of Cell Biology 2021, 220: e202009154. PMID: 33929486, PMCID: PMC8094118, DOI: 10.1083/jcb.202009154.Peer-Reviewed Original ResearchConceptsTCR signal transductionT-cell receptor pathwayLiquid-like condensatesKey adaptor proteinLAT clusteringLAT complexSH2 domainAdaptor proteinPhosphatase CD45Signal transductionTCR pathwayPhospholipase Cγ1ERK activationProtein compositionBiophysical principlesPLCγ1Critical functionsReceptor pathwayPathwayLATMajor componentT cellsCellsActivationDephosphorylation
2020
Signalling through cerebral cavernous malformation protein networks
Su VL, Calderwood DA. Signalling through cerebral cavernous malformation protein networks. Open Biology 2020, 10: 200263. PMID: 33234067, PMCID: PMC7729028, DOI: 10.1098/rsob.200263.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCarrier ProteinsDisease ManagementDisease SusceptibilityGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansIntracellular SpaceMutationProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingProtein Interaction MapsProtein TransportSignal TransductionConceptsCCM proteinsCerebral cavernous malformationsCell junctionalMEKK3-MEK5Protein complexesAdaptor proteinProtein functionSubcellular localizationCytoskeletal reorganizationComplex proteinsProtein networkRhoA-ROCKMolecular basisProtein activityGene expressionFunction mutationsCell adhesionCell contractilityProteinPathwayLeaky blood vesselsCurrent knowledgeDisease pathologyCdc42Recent advancesThe Structures of SctK and SctD from Pseudomonas aeruginosa Reveal the Interface of the Type III Secretion System Basal Body and Sorting Platform
Muthuramalingam M, Whittier SK, Lovell S, Battaile KP, Tachiyama S, Johnson DK, Picking WL, Picking WD. The Structures of SctK and SctD from Pseudomonas aeruginosa Reveal the Interface of the Type III Secretion System Basal Body and Sorting Platform. Journal Of Molecular Biology 2020, 432: 166693. PMID: 33122003, PMCID: PMC10550303, DOI: 10.1016/j.jmb.2020.10.027.Peer-Reviewed Original ResearchConceptsInner membrane ringBasal bodiesCytoplasmic domainSorting platformFirst high-resolution structureType III secretion systemCytoplasmic sorting platformTwo-hybrid analysisGram-negative bacterial pathogensProtein family membersNormal cellular functionHigh-resolution structuresAtomic resolution modelsHelix-rich structureEukaryotic cellsT3SS apparatusAdaptor proteinCellular functionsSecretion systemMembrane ringMechanistic interfaceTip complexExternal needleRadial spokesProteinSerine phosphorylation of the small phosphoprotein ICAP1 inhibits its nuclear accumulation
Su VL, Simon B, Draheim KM, Calderwood DA. Serine phosphorylation of the small phosphoprotein ICAP1 inhibits its nuclear accumulation. Journal Of Biological Chemistry 2020, 295: 3269-3284. PMID: 32005669, PMCID: PMC7062153, DOI: 10.1074/jbc.ra119.009794.Peer-Reviewed Original ResearchConceptsIntegrin cytoplasmic domain-associated protein-1N-terminal regionNuclear accumulationP21-activated kinase 4Ser-10Nuclear roleSerine phosphorylationNuclear localizationPhosphorylation-mimicking substitutionsNuclear localization signalCell-cell junctionsSer-25Localization signalKRIT1 functionThreonine residuesAdaptor proteinKRIT1 lossSubcellular localizationNeurovascular dysplasiaBlood vessel integrityVascular developmentKinase 4Cultured cellsPhosphorylationProtein 1Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination
Zhou L, Shao C, Xie Y, Wang N, Xu S, Luo B, Wu Z, Ke Y, Qiu M, Shen Y. Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination. ELife 2020, 9: e52056. PMID: 31944179, PMCID: PMC6984811, DOI: 10.7554/elife.52056.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCateninsCell DifferentiationCell LineageCentral Nervous SystemGene Expression RegulationMiceMice, KnockoutOligodendrocyte Precursor CellsOligodendrogliaPlatelet-Derived Growth FactorProtein-Tyrosine KinasesReceptors, Growth FactorRNA, Small InterferingSignal TransductionTranscription FactorsTranscriptomeConceptsPlatelet-derived growth factorCentral nervous system myelinDownstream targetsPlatelet-derived growth factor stimulationPDGF SignalingPlatelet-derived growth factor signalingReceptor tyrosine kinasesAdaptor proteinCentral nervous system hypomyelinationGab1Nuclear accumulationOligodendrocyte precursor cellsTyrosine kinaseCentral nervous systemOligodendrocyte precursor cell differentiationConditional deletionOL lineage cellsOligodendrocyte differentiationDifferentiationSteady-state numberB-cateninPrecursor cellsLineage cellsTrophic supportGrowth factor
2019
cindr, the Drosophila Homolog of the CD2AP Alzheimer’s Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis
Ojelade S, Lee T, Giagtzoglou N, Yu L, Ugur B, Li Y, Duraine L, Zuo Z, Petyuk V, De Jager P, Bennett D, Arenkiel B, Bellen H, Shulman J. cindr, the Drosophila Homolog of the CD2AP Alzheimer’s Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis. Cell Reports 2019, 28: 1799-1813.e5. PMID: 31412248, PMCID: PMC6703184, DOI: 10.1016/j.celrep.2019.07.041.Peer-Reviewed Original ResearchConceptsPlasma membrane calcium ATPaseDisease risk genesDisease susceptibility genesSynaptic vesicle recyclingUbiquitin-proteasome systemMembrane calcium ATPaseAlzheimer’s disease risk genesDrosophila homologConserved roleAlzheimer's disease susceptibility genesSynaptic proteostasisAdaptor proteinNeuronal requirementsVesicle recyclingProteostasisCindrRisk genesSusceptibility genesSynapse maturationHuman postmortem brainHuman tauProtein levelsNeurofibrillary tangle pathologyNull miceAD susceptibility
2018
Dstac is required for normal circadian activity rhythms in Drosophila
Hsu IU, Linsley JW, Varineau JE, Shafer OT, Kuwada JY. Dstac is required for normal circadian activity rhythms in Drosophila. Chronobiology International 2018, 35: 1016-1026. PMID: 29621409, PMCID: PMC6103890, DOI: 10.1080/07420528.2018.1454937.Peer-Reviewed Original ResearchConceptsPigment Dispersing FactorS-LNSmall ventrolateral neuronsBrain of DrosophilaL-type voltage-gated CaCircadian activityNovel genesAdaptor proteinCircadian locomotionVoltage-gated CaActivity rhythmsDrosophilaDmca1DGenesVentrolateral neuronsCircadian activity rhythmsVertebratesSTAC3ProteinBindsCACHActivity
2017
Neferine, is not inducer but blocker for macroautophagic flux targeting on lysosome malfunction
Xu T, Singh D, Liu J, Li H, Peng S, Rizzolo LJ, Wang SB. Neferine, is not inducer but blocker for macroautophagic flux targeting on lysosome malfunction. Biochemical And Biophysical Research Communications 2017, 495: 1516-1521. PMID: 29197576, DOI: 10.1016/j.bbrc.2017.11.169.Peer-Reviewed Original ResearchConceptsLC3-IIMultiple pharmacological effectsAMPK/mTORNeferine treatmentKnockdown of ATG5Pharmacological effectsCancer cellsNeferineStrong inducerAutophagic fluxCathepsin DPhagocytic cargoLysosome maturationLysosome malfunctionExposureMacroautophagic fluxInducerMaturationAdaptor proteinArrhythmiasBlockersCancerBreast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo
Yao C, Yu KP, Philbrick W, Sun BH, Simpson C, Zhang C, Insogna K. Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo. International Journal Of Molecular Medicine 2017, 40: 1067-1077. PMID: 28791343, PMCID: PMC5593463, DOI: 10.3892/ijmm.2017.3091.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBone ResorptionCathepsin KCell LineFemaleFemurFibroblastsGene Expression RegulationHEK293 CellsHeLa CellsHumansMaleMiceMice, Inbred C57BLMice, TransgenicNeuropeptidesNF-kappa BOrgan SpecificityOsteoclastsPromoter Regions, Geneticrac1 GTP-Binding ProteinRANK LigandSignal TransductionTibiaConceptsNF-κB signalingCell type-dependent roleCritical downstream targetNF-κBCanonical NF-κB signalingNuclear factorReceptor activatorNuclear Rac1Adaptor proteinCancer-associated genesMature osteoclast formationSmall GTPaseDownstream targetsExogenous receptor activatorLow-dose RANKLNF-κB interactionTransgenic animalsImportant regulatorBreast cancer-associated genesWild-type littermatesCell typesRac1SignalingBCA3Dependent roleCryo-EM Reveals How Human Cytoplasmic Dynein Is Auto-inhibited and Activated
Zhang K, Foster HE, Rondelet A, Lacey SE, Bahi-Buisson N, Bird AW, Carter AP. Cryo-EM Reveals How Human Cytoplasmic Dynein Is Auto-inhibited and Activated. Cell 2017, 169: 1303-1314.e18. PMID: 28602352, PMCID: PMC5473941, DOI: 10.1016/j.cell.2017.05.025.Peer-Reviewed Original ResearchConceptsStructure-based mutagenesisCryoelectron microscopy structureCargo adaptor proteinsMicroscopy structureAdaptor proteinCytoplasmic dyneinMicrotubule affinityCryo-EMDynein 1DynactinOpen formDynein tailInhibited stateProcessive movementMotor domainMicrotubulesMotor dimerizationTransport machinesHigh affinityMutagenesisDyneinTailAffinityProteinDimerization
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