2022
Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling
Marcogliese P, Dutta D, Ray S, Dang N, Zuo Z, Wang Y, Lu D, Fazal F, Ravenscroft T, Chung H, Kanca O, Wan J, Douine E, Network U, Pena L, Yamamoto S, Nelson S, Might M, Meyer K, Yeo N, Bellen H. Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling. Science Advances 2022, 8: eabl5613. PMID: 35044823, PMCID: PMC8769555, DOI: 10.1126/sciadv.abl5613.Peer-Reviewed Original ResearchConceptsAxonal lossPatient-derived astrocytesChildhood-onset neurodegenerative disordersNeuronal depletionNeural dysfunctionNeuronal expressionNeurological defectsPharmacological inhibitionNeurodegenerative disordersNeuronal maintenanceNeurological phenotypeWnt antagonistsDownstream signalingIRF2BPLBinding proteinInhibitionWntSignalingWnt transcriptionAstrocytesDysfunctionAntagonistBrain
2019
Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification
Şentürk M, Lin G, Zuo Z, Mao D, Watson E, Mikos A, Bellen H. Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification. Nature Cell Biology 2019, 21: 384-396. PMID: 30804504, PMCID: PMC6534127, DOI: 10.1038/s41556-019-0281-x.Peer-Reviewed Original ResearchMeSH KeywordsAmyotrophic Lateral SclerosisAnimalsAnimals, Genetically ModifiedAutophagyCarrier ProteinsCell Cycle ProteinsDrosophila melanogasterDrosophila ProteinsGene Expression Regulation, DevelopmentalHEK293 CellsHumansHydrogen-Ion ConcentrationLysosomesMutationNervous SystemSignal TransductionTOR Serine-Threonine KinasesConceptsAutophagic fluxDefective autophagic fluxEndoplasmic reticulum stressReticulum stressRegulator of autophagyConserved roleAmyotrophic lateral sclerosisMammalian cellsProteasomal degradationImpaired proteostasisDemise of neuronsUbiquilinLysosome acidificationFamilial amyotrophic lateral sclerosisLysosomal acidificationATPase activityMTORMutantsAutophagyDrosophilaProteostasisAcidificationCommon featureGenesLateral sclerosisVAMP 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
2016
WAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes
David-Morrison G, Xu Z, Rui Y, Charng W, Jaiswal M, Yamamoto S, Xiong B, Zhang K, Sandoval H, Duraine L, Zuo Z, Zhang S, Bellen H. WAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes. Developmental Cell 2016, 36: 139-151. PMID: 26812014, PMCID: PMC4730548, DOI: 10.1016/j.devcel.2015.12.019.Peer-Reviewed Original ResearchConceptsPontin/Reptin complexMTOR activityRapamycin complex 1Energy statusRegulation of metabolismEnergy-dependent activationDrosophila screenEnergy-dependent mannerTTT complexRAG interactionsMTORC1 activityMechanistic targetReptinPhysical interactionRegulatorDimerizationNeuronal dysfunctionComplexesPontinHomologActivationComplexes 1AdaptorAutophagyMTOR