2019
PQLC2 recruits the C9orf72 complex to lysosomes in response to cationic amino acid starvation
Amick J, Tharkeshwar AK, Talaia G, Ferguson SM. PQLC2 recruits the C9orf72 complex to lysosomes in response to cationic amino acid starvation. Journal Of Cell Biology 2019, 219: e201906076. PMID: 31851326, PMCID: PMC7039192, DOI: 10.1083/jcb.201906076.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Transport Systems, BasicAmino AcidsAutophagyC9orf72 ProteinHEK293 CellsHumansLysosomesMechanistic Target of Rapamycin Complex 1Protein Interaction Domains and MotifsConceptsC9orf72 complexAmino acidsNormal lysosome functionAmino acid-sensing mechanismAmino acid starvationMembrane of lysosomesRegulated recruitmentComplex recruitmentCationic amino acidsHeterotrimeric complexPQLC2Acid-sensing mechanismsBinding partnerC9orf72 proteinComplex abundanceLysosome functionNovel mechanismLysosomesWDR41New roleComplexesRecruitmentSMCR8AcidProteinWeak 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 ResearchMeSH KeywordsBiophysical PhenomenaC9orf72 ProteinCarrier ProteinsHEK293 CellsHeLa CellsHumansLysosomesMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesMutationPhenotypeProteinsTOR Serine-Threonine KinasesConceptsAmino acid availabilityAcid availabilityGenome-editing strategiesKO cell linesProtein complexesSubcellular localizationKnockout phenotypesC9orf72 proteinLysosomal siteBioinformatics predictionSMCR8Tumor suppressorSwollen lysosomesFunctional interactionLysosomesC9orf72 geneCell linesStructural similarityNormal functionC9orf72PhenotypeAmyotrophic lateral sclerosisBirt-HoggIntronsMTORC1
2013
Recruitment of folliculin to lysosomes supports the amino acid–dependent activation of Rag GTPases
Petit CS, Roczniak-Ferguson A, Ferguson SM. Recruitment of folliculin to lysosomes supports the amino acid–dependent activation of Rag GTPases. Journal Of Cell Biology 2013, 202: 1107-1122. PMID: 24081491, PMCID: PMC3787382, DOI: 10.1083/jcb.201307084.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBlotting, WesternCarrier ProteinsCytoplasmFluorescent Antibody TechniqueHumansImmunoprecipitationLysosomesMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsMultiprotein ComplexesProto-Oncogene ProteinsRecombinant ProteinsRNA, Small InterferingTOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsAmino acid-dependent activationAcid-dependent activationTranscription factor EBRag GTPasesSurface of lysosomesMTORC1-dependent phosphorylationAmino acid depletionLysosome recruitmentGTPase domainRAG interactionsCytoplasmic sequestrationLysosome functionGTPasesFLCNHuman diseasesFunction mutationsDevelopment of pneumothoraxProtein 1Direct interactionLysosomesCritical rolePulmonary cystsSite of actionAcid depletionFolliculin gene
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