2019
Maturation and Clearance of Autophagosomes in Neurons Depends on a Specific Cysteine Protease Isoform, ATG-4.2
Hill SE, Kauffman KJ, Krout M, Richmond JE, Melia TJ, Colón-Ramos DA. Maturation and Clearance of Autophagosomes in Neurons Depends on a Specific Cysteine Protease Isoform, ATG-4.2. Developmental Cell 2019, 49: 251-266.e8. PMID: 30880001, PMCID: PMC6482087, DOI: 10.1016/j.devcel.2019.02.013.Peer-Reviewed Original ResearchConceptsGenetic screenForward genetic screenClearance of autophagosomesProtease isoformsAutophagosomesCell bodiesAutophagosome clearanceSynaptic materialNeurodegenerative diseasesMaturationRetrograde transportNeuronal activityAbnormal accumulationNeuronsSingle neuronsClearanceGABARAPVivoTraffickingAutophagyScreenIsoformsMechanismMembraneSynapse
2018
Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases
Kauffman KJ, Yu S, Jin J, Mugo B, Nguyen N, O'Brien A, Nag S, Lystad AH, Melia TJ. Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases. Autophagy 2018, 14: 992-1010. PMID: 29458288, PMCID: PMC6103404, DOI: 10.1080/15548627.2018.1437341.Peer-Reviewed Original ResearchConceptsAtg8-family proteinsAtg4 proteasesATG8 proteinsMammalian Atg8 proteinsMacroautophagy/autophagySimilar enzymatic activityProteolytic processing eventsLIR motifATG4 familyProcessing eventsPhysical anchoringProteinEnzymatic activityProteaseSoluble substratesATG4BTerminal glycinePhagophoreHomologLipidsDelipidationAutophagosomesAutophagyMotifSubstrate
2014
Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3
Nath S, Dancourt J, Shteyn V, Puente G, Fong WM, Nag S, Bewersdorf J, Yamamoto A, Antonny B, Melia TJ. Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3. Nature Cell Biology 2014, 16: 415-424. PMID: 24747438, PMCID: PMC4111135, DOI: 10.1038/ncb2940.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid MotifsAnimalsApoptosis Regulatory ProteinsAutophagy-Related Protein 7Autophagy-Related Protein 8 FamilyAutophagy-Related ProteinsCell MembraneCytoskeletal ProteinsHeLa CellsHumansHydrophobic and Hydrophilic InteractionsLiposomesMembrane ProteinsMiceMice, KnockoutMicrofilament ProteinsMicrotubule-Associated ProteinsMutationPhosphatidylethanolaminesRatsSignal TransductionStress, PhysiologicalTransfectionUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesConceptsLipid-packing defectsLC3/GABARAP familyLC3/GABARAP lipidationAmino-terminal amphipathic helixE2-like enzymeGABARAP familyAutophagic machineryIsolation membraneAmphipathic helixIntracellular membranesAutophagy proteinsRescue experimentsATG3LipidationCurved rimProteinMotifPhysiologic roleMembranePhagophoreAutophagosomesMachineryHelixEnzyme
2012
The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation
Choy A, Dancourt J, Mugo B, O’Connor T, Isberg RR, Melia TJ, Roy CR. The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation. Science 2012, 338: 1072-1076. PMID: 23112293, PMCID: PMC3682818, DOI: 10.1126/science.1227026.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAutophagyAutophagy-Related Protein 7Autophagy-Related Protein 8 FamilyAutophagy-Related ProteinsBacterial ProteinsCell Culture TechniquesCysteine ProteasesGene DeletionGlycineHEK293 CellsHost-Pathogen InteractionsHumansHydrolysisLegionella pneumophilaLegionnaires' DiseaseMicrofilament ProteinsPhagosomesUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesConceptsATG8 proteinsIntracellular pathogen Legionella pneumophilaPathogen Legionella pneumophilaAdjacent aromatic residuesCarboxyl-terminal glycine residueAutophagosome membraneEukaryotic cellsAutophagy pathwayGlycine residueAromatic residuesIntracellular pathogensRavZAutophagyProteinLegionella pneumophilaSpecific mechanismsResiduesPathogensATG3MicrobesAtg7CytosolVacuolesPathwayPneumophila