2025
LRRK2, lysosome damage, and Parkinson's disease
Bentley-DeSousa A, Clegg D, Ferguson S. LRRK2, lysosome damage, and Parkinson's disease. Current Opinion In Cell Biology 2025, 93: 102482. PMID: 39983584, DOI: 10.1016/j.ceb.2025.102482.Peer-Reviewed Original ResearchConceptsLRRK2 kinase activityKinase activitySubstrate of LRRK2Rab familySmall GTPasesLysosomal biologyDamaged lysosomesEndolysosomal membranesRegulatory mechanismsNormal biologyPathogenesis of Parkinson's diseaseLRRK2Repair mechanismsLysosomal damageLysosomesBiologyGTPaseParkinson's diseaseRabGABARAPActivityA STING–CASM–GABARAP pathway activates LRRK2 at lysosomes
Bentley-DeSousa A, Roczniak-Ferguson A, Ferguson S. A STING–CASM–GABARAP pathway activates LRRK2 at lysosomes. Journal Of Cell Biology 2025, 224: e202310150. PMID: 39812709, PMCID: PMC11734622, DOI: 10.1083/jcb.202310150.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyEnzyme ActivationHEK293 CellsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LysosomesMembrane ProteinsMiceMicrotubule-Associated ProteinsProtein Serine-Threonine KinasesSignal TransductionConceptsLRRK2 kinase activityKinase activityStimulator of interferon genesKinase activity of LRRK2Protein family membersLysosomal recruitmentLysosomal homeostasisEndogenous cellular mechanismsAberrant activationLRRK2Interferon genesLysosomesSingle membraneLysosomal damageMultiple chemical stimuliKinaseCellular mechanismsPathwayFamily membersChemical stimuliGABARAPMultiple stimuliGenesMutationsActivity
2019
Maturation and Clearance of Autophagosomes in Neurons Depends on a Specific Cysteine Protease Isoform, ATG-4.2
Kargbo-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 neuronsClearanceGABARAPVivoTraffickingAutophagyScreenIsoformsMechanismMembraneSynapseDistinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes
Lystad AH, Carlsson SR, de la Ballina LR, Kauffman KJ, Nag S, Yoshimori T, Melia TJ, Simonsen A. Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. Nature Cell Biology 2019, 21: 372-383. PMID: 30778222, PMCID: PMC7032593, DOI: 10.1038/s41556-019-0274-9.Peer-Reviewed Original ResearchConceptsMembrane-binding regionTerminal membrane-binding regionLC3B lipidationMembrane-binding amphipathic helixLC3/GABARAPDifferent cellular conditionsDouble-membrane phagophoreSingle-membrane structuresGABARAP proteinsCanonical autophagyCellular conditionsAmphipathic helixTarget membraneMembrane bindingC-terminusDistinct functionsCovalent modificationLipidationΒ isoformsEssential roleKey eventsIsoformsPhagophoreGABARAPMacroautophagy
2016
Human Atg8-cardiolipin interactions in mitophagy: Specific properties of LC3B, GABARAPL2 and GABARAP
Antón Z, Landajuela A, Hervás JH, Montes LR, Hernández-Tiedra S, Velasco G, Goñi FM, Alonso A. Human Atg8-cardiolipin interactions in mitophagy: Specific properties of LC3B, GABARAPL2 and GABARAP. Autophagy 2016, 12: 2386-2403. PMID: 27764541, PMCID: PMC5172498, DOI: 10.1080/15548627.2016.1240856.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 8 FamilyCardiolipinsCell Line, TumorCell MembraneDronabinolGlioblastomaHumansHydrophobic and Hydrophilic InteractionsMicrotubule-Associated ProteinsMitochondriaMitochondrial MembranesMitophagyPressureProtein BindingRotenoneSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidConceptsSelective mitochondrial autophagyOuter mitochondrial membraneHuman Atg8Quantitative biophysical techniquesHuman orthologAutophagosome formationMitochondrial autophagyMitochondrial membraneAutophagic processC-terminusGABARAPL2GABARAPPhospholipid cardiolipinBiophysical techniquesMitochondriaOrthologsMembrane fluidityCardiolipinLC3BMitophagyPositive cooperativitySpecific roleU87MG cellsAutophagyHydrophilic environment
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