2022
ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling
Hancock-Cerutti W, Wu Z, Xu P, Yadavalli N, Leonzino M, Tharkeshwar AK, Ferguson SM, Shadel GS, De Camilli P. ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling. Journal Of Cell Biology 2022, 221: e202106046. PMID: 35657605, PMCID: PMC9170524, DOI: 10.1083/jcb.202106046.Peer-Reviewed Original ResearchConceptsParkinson's diseasePD pathogenesisLeucine-rich repeat kinase 2 (LRRK2) G2019S mutationCGAS-STING pathwayAccumulation of lysosomesDNA-sensing cGAS-STING pathwayImmune activationLipid profileSTING signalingG2019S mutationAutosomal recessive Parkinson's diseaseRecessive Parkinson's diseaseModel human cell linesHuman cell linesCell linesPathogenesisLate endosomes/lysosomesDiseaseVPS13CEndosomes/lysosomesCurrent studyTransfer proteinActivationCellsPathway
2016
C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling
Amick J, Roczniak-Ferguson A, Ferguson SM. C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling. Molecular Biology Of The Cell 2016, 27: 3040-3051. PMID: 27559131, PMCID: PMC5063613, DOI: 10.1091/mbc.e16-01-0003.Peer-Reviewed Original ResearchConceptsAmino acid availabilityAcid availabilityGenome-editing strategiesKO cell linesProtein complexesSubcellular localizationKnockout phenotypesC9orf72 proteinLysosomal siteBioinformatics predictionSMCR8Tumor suppressorSwollen lysosomesFunctional interactionLysosomesC9orf72 geneCell linesStructural similarityNormal functionC9orf72PhenotypeAmyotrophic lateral sclerosisBirt-HoggIntronsMTORC1
2012
The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis
Roczniak-Ferguson A, Petit CS, Froehlich F, Qian S, Ky J, Angarola B, Walther TC, Ferguson SM. The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis. Science Signaling 2012, 5: ra42. PMID: 22692423, PMCID: PMC3437338, DOI: 10.1126/scisignal.2002790.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsAnalysis of VarianceBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsElectrophoretic Mobility Shift AssayGene Expression RegulationHeLa CellsHomeostasisHumansLysosomesMechanistic Target of Rapamycin Complex 1Microphthalmia-Associated Transcription FactorMicroscopy, ConfocalMultiprotein ComplexesMutationPhosphorylationProteinsSignal TransductionTOR Serine-Threonine KinasesConceptsMTOR-dependent phosphorylationLysosomal functionTranscription factor MITFRapamycin complex 1Transcription factor TFEBMajor cellular siteTarget of mTORTranslocation of TFEBDefective organellesTranscriptional regulationCellular needsCellular homeostasisTranscriptional controlLysosome homeostasisLysosome biogenesisTranscription factorsLysosomal biogenesisPhysiological contextRegulatory mechanismsLysosome functionMechanistic targetTFEBCellular sitesLysosomal activityBiogenesis