2023
Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation
Chung H, Ye Q, Park Y, Zuo Z, Mok J, Kanca O, Tattikota S, Lu S, Perrimon N, Lee H, Bellen H. Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation. Cell Metabolism 2023, 35: 855-874.e5. PMID: 37084732, PMCID: PMC10160010, DOI: 10.1016/j.cmet.2023.03.022.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisAdministration of fingolimodFunctions of S1PNF-κB activationSphingosine-1-phosphate (S1P) synthesisS1P receptor antagonistsElevated VLCFAAutoimmune encephalomyelitisFatty acidsMacrophage infiltrationReceptor antagonistImmune cellsMouse modelTreatment avenuesVLCFA levelsFly gliaLong-chain fatty acidsGliaS1P pathwayS1PNeuroinflammationFingolimodVLCFAAbundant fatty acidsExploring therapeutic strategies for infantile neuronal axonal dystrophy (INAD/PARK14)
Lin G, Tepe B, McGrane G, Tipon R, Croft G, Panwala L, Hope A, Liang A, Zuo Z, Byeon S, Wang L, Pandey A, Bellen H. Exploring therapeutic strategies for infantile neuronal axonal dystrophy (INAD/PARK14). ELife 2023, 12: e82555. PMID: 36645408, PMCID: PMC9889087, DOI: 10.7554/elife.82555.Peer-Reviewed Original ResearchConceptsPatient-derived neural progenitor cellsNeural progenitor cellsPatient-derived neuronsPediatric neurodegenerative disorderRetromer functionMitochondrial morphologyEndolysosomal pathwayMitochondrial defectsProlong lifespanNeurodegenerative phenotypeProgenitor cellsMouse modelRecessive variantsNeurodegenerative disordersGene therapy approachesPathwayInfantile neuroaxonal dystrophyHomologCellsTherapeutic strategiesAzoramidePurkinje cellsFliesPhenotypeMetabolism
2022
Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin
Cristobal C, Wang C, Zuo Z, Smith J, Lindeke-Myers A, Bellen H, Lee H. Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin. Journal Of Neuroscience 2022, 42: 1679-1691. PMID: 35101966, PMCID: PMC8896627, DOI: 10.1523/jneurosci.1517-21.2022.Peer-Reviewed Original ResearchConceptsGelsolin levelsOL differentiationMyelin sheathCNS functionMorphogenesis 2Motor coordination deficitsActin cytoskeletonWhite matter diseaseMyelin structureConditional knockout miceWhite matter developmentMyelin compactionMyelin decompactionNeuronal healthCKO miceCoordination deficitsFunctional myelinCompact myelin sheathKnockout miceWhite matterPostnatal developmentProper myelin formationOligodendrocytesMyelin formationOL cultures
2020
The Daam2–VHL–Nedd4 axis governs developmental and regenerative oligodendrocyte differentiation
Ding X, Jo J, Wang C, Cristobal C, Zuo Z, Ye Q, Wirianto M, Lindeke-Myers A, Choi J, Mohila C, Kawabe H, Jung S, Bellen H, Yoo S, Lee H. The Daam2–VHL–Nedd4 axis governs developmental and regenerative oligodendrocyte differentiation. Genes & Development 2020, 34: 1177-1189. PMID: 32792353, PMCID: PMC7462057, DOI: 10.1101/gad.338046.120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationGene Expression Regulation, DevelopmentalHumansMiceMice, KnockoutMicrofilament ProteinsMultiple SclerosisMyelin SheathNedd4 Ubiquitin Protein LigasesNerve RegenerationNervous System DiseasesOligodendrogliaProtein StabilityRho GTP-Binding ProteinsUbiquitinationVon Hippel-Lindau Tumor Suppressor ProteinConceptsWhite matter injuryUbiquitin-proteasomal systemGenetic knockout mouse modelsOligodendrocyte differentiationWhite matter lesionsKnockout mouse modelDemyelination modelMultiple sclerosisDisease-driving proteinsMatter lesionsOligodendrocyte dysfunctionPathogenic accumulationMouse modelDevelopmental myelinationNeurological disordersGlial biologyOligodendrocyte developmentE3 ligase VHLVHLRepairE3 ubiquitinProteomic analysisRemyelinationSclerosisPatientsNovel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue
Li X, Yang L, Mao Z, Pan X, Zhao Y, Gu X, Eckel‐Mahan K, Zuo Z, Tong Q, Hartig S, Cheng X, Du G, Moore D, Bellen H, Sesaki H, Sun K. Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue. The FASEB Journal 2020, 34: 8265-8282. PMID: 32294302, PMCID: PMC7336545, DOI: 10.1096/fj.201903100rr.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumFlx/Function of Drp1Multicellular organismsPeroxisomal fissionDrp1 ablationER retentionLD dynamicsAutophagy functionER functionNovel roleDrp1LD morphologyKnockout modelsProtein 1Unilocular morphologyAdipose tissueLipid metabolismDynaminOrganellesCold exposureTissueOrganismsLarge sizeMultilocular structureLoss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms
Chung H, Wangler M, Marcogliese P, Jo J, Ravenscroft T, Zuo Z, Duraine L, Sadeghzadeh S, Li-Kroeger D, Schmidt R, Pestronk A, Rosenfeld J, Burrage L, Herndon M, Chen S, Network M, Shillington A, Vawter-Lee M, Hopkin R, Rodriguez-Smith J, Henrickson M, Lee B, Moser A, Jones R, Watkins P, Yoo T, Mar S, Choi M, Bucelli R, Yamamoto S, Lee H, Prada C, Chae J, Vogel T, Bellen H. Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron 2020, 106: 589-606.e6. PMID: 32169171, PMCID: PMC7289150, DOI: 10.1016/j.neuron.2020.02.021.Peer-Reviewed Original ResearchConceptsSchwann cellsAxonal lossMurine Schwann cellsPrimary Schwann cellsTreatment of fliesLong-chain fatty acid β-oxidation pathwayNeuronal lossGlial lossSynaptic transmissionRate-limiting enzymeDevelopmental delayACOX1Elevated levelsFatty acid β-oxidation pathwayReactive oxygen speciesDifferent mechanismsPupal deathPatientsDominant variantFunction mutationsGliaOxygen speciesTreatmentDe novoCells
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 susceptibilityVAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway
Mao D, Lin G, Tepe B, Zuo Z, Tan K, Senturk M, Zhang S, Arenkiel B, Sardiello M, Bellen H. VAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway. Autophagy 2019, 15: 1214-1233. PMID: 30741620, PMCID: PMC6613884, DOI: 10.1080/15548627.2019.1580103.Peer-Reviewed Original ResearchAnimalsAutophagosomesAutophagyCarrier ProteinsDrosophilaDrosophila ProteinsEIF-2 KinaseEndoplasmic ReticulumEndosomesGolgi ApparatusHEK293 CellsHeLa CellsHumansLysosomal-Associated Membrane Protein 2LysosomesMembrane ProteinsMiceMice, Inbred C57BLMutationPhosphatidylinositol PhosphatesR-SNARE ProteinsRab GTP-Binding ProteinsRab7 GTP-Binding ProteinsVesicular Transport ProteinsMolecular layer interneurons shape the spike activity of cerebellar Purkinje cells
Brown A, Arancillo M, Lin T, Catt D, Zhou J, Lackey E, Stay T, Zuo Z, White J, Sillitoe R. Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells. Scientific Reports 2019, 9: 1742. PMID: 30742002, PMCID: PMC6370775, DOI: 10.1038/s41598-018-38264-1.Peer-Reviewed Original ResearchConceptsMolecular layer interneuronsPurkinje cellsGABAergic neurotransmissionSpike firingVesicular GABA transporterClasses of interneuronsPurkinje cell functionCerebellar Purkinje cellsComplex spike firingPurkinje cell activityPurkinje cell simple spike firingInhibitory molecular layer interneuronsConditional genetic approachPurkinje cell simple spikesSynaptic inputsStellate cellsSpike activitySimple spike firingFiring propertiesGABA transporterCell activityInterneuronsSelective depletionCell functionComplex spikes