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
2021
Efficient progranulin exit from the ER requires its interaction with prosaposin, a Surf4 cargo
Devireddy S, Ferguson SM. Efficient progranulin exit from the ER requires its interaction with prosaposin, a Surf4 cargo. Journal Of Cell Biology 2021, 221: e202104044. PMID: 34919127, PMCID: PMC8689666, DOI: 10.1083/jcb.202104044.Peer-Reviewed Original ResearchTSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism
Alesi N, Akl EW, Khabibullin D, Liu HJ, Nidhiry AS, Garner ER, Filippakis H, Lam HC, Shi W, Viswanathan SR, Morroni M, Ferguson SM, Henske EP. TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism. Nature Communications 2021, 12: 4245. PMID: 34253722, PMCID: PMC8275687, DOI: 10.1038/s41467-021-24499-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarcinoma, Renal CellCell NucleusCell ProliferationFemaleGene Expression RegulationHEK293 CellsHeLa CellsHumansKidney NeoplasmsLysosomesMiceMice, Inbred NODMice, SCIDMonomeric GTP-Binding ProteinsOrganelle BiogenesisPhosphorylationPhosphoserineProtein TransportProto-Oncogene ProteinsTranscription, GeneticTuberous Sclerosis Complex 2 ProteinTumor Suppressor ProteinsConceptsTranscription factor EBTSC2-deficient cellsLysosome biogenesisLysosomal biogenesisDeficient cellsRapamycin complex 1TSC1/2 complexTFEB phosphorylationTuberous sclerosis complexTSC proteinsMaster regulatorBiogenesisMechanistic targetRagCCritical regulatorFolliculinPhosphorylationDependent sitesRegulatorProteinOverexpressionTSC2 mutationsCellsGTPaseMTORC1
2019
Weak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment
Angarola B, Ferguson SM. Weak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment. Molecular Biology Of The Cell 2019, 30: 2750-2760. PMID: 31532697, PMCID: PMC6789162, DOI: 10.1091/mbc.e19-03-0146.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsChlorocebus aethiopsCOS CellsEndoplasmic ReticulumHeLa CellsHumansLysosomesMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsMultiprotein ComplexesNeuropeptidesPrenylationRas Homolog Enriched in Brain ProteinSignal TransductionTOR Serine-Threonine KinasesConceptsMembrane interactionsC-terminal CAAX motifTransient membrane interactionsEndoplasmic reticulum localizationMTOR complex 1CAAX motifRheb GTPaseER membraneMTORC1 activationSubcellular localizationTargeting motifRhebLysosome enrichmentHuman cellsFunctional assaysTargeting mechanismStable interactionStable localizationLysosomesFurther systematic analysisMotifActivation
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