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
VAMP 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 PhosphatesRab GTP-Binding ProteinsRab7 GTP-Binding ProteinsR-SNARE ProteinsVesicular Transport Proteins
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