2020
TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS
Cunningham K, Maulding K, Ruan K, Senturk M, Grima J, Sung H, Zuo Z, Song H, Gao J, Dubey S, Rothstein J, Zhang K, Bellen H, Lloyd T. TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS. ELife 2020, 9: e59419. PMID: 33300868, PMCID: PMC7758070, DOI: 10.7554/elife.59419.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAmyotrophic Lateral SclerosisAnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBlotting, WesternC9orf72 ProteinDisease Models, AnimalDrosophila melanogasterFemaleFluorescent Antibody TechniqueFrontotemporal DementiaHeLa CellsHumansLysosomesMaleMicrophthalmia-Associated Transcription FactorMicroscopy, Electron, TransmissionMotor CortexConceptsNucleocytoplasmic transportNuclear importC9-ALS/FTDKey transcriptional regulatorAutophagic cargo degradationNeurodegenerative disease pathogenesisLysosome-like organellesProteostasis defectsGGGGCC hexanucleotide repeat expansionTranscriptional regulatorsCargo degradationKey regulatorUbiquitinated aggregatesCytoplasmic mislocalizationHuman cellsAmyotrophic lateral sclerosisGGGGCC repeatsHexanucleotide repeat expansionRepeat expansionFrontotemporal dementiaTFEBC9-ALSAutophagyRegulatorPotent suppressor
2019
Loss of Oxidation Resistance 1, OXR1, Is Associated with an Autosomal-Recessive Neurological Disease with Cerebellar Atrophy and Lysosomal Dysfunction
Wang J, Rousseau J, Kim E, Ehresmann S, Cheng Y, Duraine L, Zuo Z, Park Y, Li-Kroeger D, Bi W, Wong L, Rosenfeld J, Gleeson J, Faqeih E, Alkuraya F, Wierenga K, Chen J, Afenjar A, Nava C, Doummar D, Keren B, Juusola J, Grompe M, Bellen H, Campeau P. Loss of Oxidation Resistance 1, OXR1, Is Associated with an Autosomal-Recessive Neurological Disease with Cerebellar Atrophy and Lysosomal Dysfunction. American Journal Of Human Genetics 2019, 105: 1237-1253. PMID: 31785787, PMCID: PMC6904826, DOI: 10.1016/j.ajhg.2019.11.002.Peer-Reviewed Original Researchcindr, 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
Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain
Lin G, Lee P, Chen K, Mao D, Tan K, Zuo Z, Lin W, Wang L, Bellen H. Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain. Cell Metabolism 2018, 28: 605-618.e6. PMID: 29909971, DOI: 10.1016/j.cmet.2018.05.019.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-SynucleinAnimalsBrainCell Line, TumorCeramidesDrosophilaDrosophila ProteinsFeedback, PhysiologicalFemaleGroup VI Phospholipases A2Group X Phospholipases A2HeLa CellsHumansLysosomesMaleMembrane FluidityMutationNeuronsNuclear ProteinsParkinson DiseaseRNA-Binding ProteinsSphingolipidsVesicular Transport ProteinsConceptsIPLA2-VIAImpairs synaptic transmissionEarly-onset parkinsonismSynaptic transmissionNeuroaxonal dystrophyParkinson's diseaseNeuronal functionBrain tissueNeurodegenerative disordersΑ-synucleinPLA2G6Ceramide levelsProgressive increaseNeurodegenerationLysosomal stressPositive feedback loopRetromer functionPhospholipid compositionCeramideGlycerol phospholipidsParkinsonismVPS35Desipramine
2017
Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially
Luo X, Rosenfeld J, Yamamoto S, Harel T, Zuo Z, Hall M, Wierenga K, Pastore M, Bartholomew D, Delgado M, Rotenberg J, Lewis R, Emrick L, Bacino C, Eldomery M, Coban Akdemir Z, Xia F, Yang Y, Lalani S, Lotze T, Lupski J, Lee B, Bellen H, Wangler M, . Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially. PLOS Genetics 2017, 13: e1006905. PMID: 28742085, PMCID: PMC5557584, DOI: 10.1371/journal.pgen.1006905.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnimals, Genetically ModifiedCalcium ChannelsCerebellar AtaxiaChildChild, PreschoolDrosophila melanogasterFemaleGenome, HumanGenome-Wide Association StudyHumansMaleMicroscopy, Electron, TransmissionMutation, MissenseNeurodegenerative DiseasesNeuroimagingPhenotypePoint MutationConceptsNeurodegenerative phenotypeGenomic rescue constructsS4 transmembrane segmentRescue constructTransmembrane segmentsFunction phenotypesLoss of functionMissense allelesFunction allelesWild typeGlobal developmental delayToxic gainMutant clonesDominant mutationsDevelopmental delayPoint mutationsDrosophilaFunctional impactPhenotypeQ-type voltage-dependent Ca2Early-onset developmental delayNeurological phenotypeAllelesSynaptic functionNovel variants
2016
Uncoupling neuronal death and dysfunction in Drosophila models of neurodegenerative disease
Chouhan A, Guo C, Hsieh Y, Ye H, Senturk M, Zuo Z, Li Y, Chatterjee S, Botas J, Jackson G, Bellen H, Shulman J. Uncoupling neuronal death and dysfunction in Drosophila models of neurodegenerative disease. Acta Neuropathologica Communications 2016, 4: 62. PMID: 27338814, PMCID: PMC4918017, DOI: 10.1186/s40478-016-0333-4.Peer-Reviewed Original ResearchMeSH KeywordsAgingAlpha-SynucleinAmyloid beta-PeptidesAnimalsAnimals, Genetically ModifiedCell DeathDisease Models, AnimalDrosophilaElectroretinographyFemaleHumansMembrane PotentialsMicroelectrodesMicroscopy, Electron, TransmissionNeurodegenerative DiseasesNeuronsPeptide FragmentsRetinaTau ProteinsVision, OcularConceptsAdult Drosophila retinaToxic protein speciesDisease-relevant proteinsMicrotubule-associated protein tauMedium-throughput assaysProgressive photoreceptor cell deathCodon-optimized transgeneCommon neurodegenerative proteinopathiesAdult nervous systemDrosophila retinaNeuronal deathProtein speciesGlial cell typesDrosophila modelParkinson's diseaseNervous systemAlzheimer's diseaseAge-dependent neuronal lossPhotoreceptor cell deathCell deathCell typesProtein tauDrosophilaExpression of tauPotential degenerative changesRab8 directs furrow ingression and membrane addition during epithelial formation in Drosophila melanogaster
Mavor L, Miao H, Zuo Z, Holly R, Xie Y, Loerke D, Blankenship J. Rab8 directs furrow ingression and membrane addition during epithelial formation in Drosophila melanogaster. Development 2016, 143: 892-903. PMID: 26839362, PMCID: PMC4813336, DOI: 10.1242/dev.128876.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAnimals, Genetically ModifiedCell MembraneCRISPR-Cas SystemsCrosses, GeneticCytoplasmDrosophila melanogasterDrosophila ProteinsEmbryo, NonmammalianEpitheliumExocytosisFemaleGene Expression Regulation, DevelopmentalGolgi ApparatusGTP PhosphohydrolasesGuanosine TriphosphateMaleMembrane ProteinsMicroscopy, ConfocalProtein Structure, TertiaryRab GTP-Binding ProteinsConceptsFurrow ingressionMembrane additionPlasma membranePlasma membrane furrowsLarge cytoplasmic aggregatesCRISPR/Cas9 technologyIntracellular trafficking pathwaysMembrane furrowsRab8 functionDrosophila embryosDrosophila melanogasterTrafficking pathwaysMembrane compartmentsEndogenous localizationProtein Rab11Early embryosCytoplasmic aggregatesCas9 technologyRab8Membrane storesCell surfaceEpithelial sheetsRab11Cell morphologyCompartmental behavior